J Neurogastroenterol Motil 2024; 30(4): 453-458  https://doi.org/10.5056/jnm23149
Additional Diagnostic Yield of the Rapid Drink Challenge in Chicago Classification Version 4.0 Compared With Version 3.0
Hoyoung Wang,1 Kee Wook Jung,2* Jin Hee Noh,2 Hee Kyoung Na,2 Ji Yong Ahn,2 Jeong Hoon Lee,2 Do Hoon Kim,2 Kee Don Choi,2 Ho June Song,2 Gin Hyug Lee,2 and Hwoon-Yong Jung2
1Department of Gastroenterology, Ulsan University Hospital, University of Ulsan College of Medicine, Seoul, Korea; and 2Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Correspondence to: *Kee Wook Jung, MD, PhD
Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
Tel: +82-2-3010-3900, E-mail: jung.keewook30@gmail.com
Received: September 19, 2023; Revised: December 6, 2023; Accepted: February 27, 2024; Published online: October 30, 2024
© 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
Chicago classification version 4.0 enhances the diagnosis of esophageal motility disorders using position change and provocative tests such as multiple rapid swallows and a rapid drink challenge. This study investigates the diagnostic role of the rapid drink challenge based on Chicago classification 4.0 using a functional luminal imaging probe to estimate the cutoff value.
Methods
This study included 570 patients who underwent esophageal manometry with a rapid drink challenge between January 2019 and October 2022. The diagnostic flow was analyzed according to Chicago classification 4.0.
Results
Ninety-nine patients (38, achalasia; 11, esophagogastric junction outflow obstruction; 7, ineffective esophageal motility; 1, hypercontractile esophagus; and 42, normal esophageal function) failed the rapid drink challenge. Among the 453 participants, 50 and 86 were diagnosed with achalasia and esophagogastric junction outflow obstruction, respectively, using Chicago classification 4.0. In 249/453 (55.0%) patients initially diagnosed with esophagogastric junction outflow obstruction using Chicago classification 3.0, the diagnosis was changed to achalasia (n = 28), hypercontractile esophagus (n = 7), ineffective esophageal motility (n = 7), or normal esophageal function (n = 121) using Chicago classification 4.0. Rapid drink challenge-integrated relaxation pressure’s diagnostic cutoff value was 19 mmHg. Nine patients had diagnoses changed after the rapid drink challenge, including 3 with panesophageal pressurization.
Conclusions
Chicago classification 4.0 increased the diagnostic yield of the rapid drink challenge by 2.0% (9/453 patients). However, the rapid drink challenge had a failure rate of 17.9% (99/552 patients). Given the relatively low diagnostic yield and high failure rate of the rapid drink challenge, we recommend adopting an individualized approach to manometry.
Keywords: Esophageal achalasia; Esophageal motility disorders; Manometry
Introduction

High-resolution manometry (HRM) is a crucial tool for visualizing esophageal pressure in order to diagnose esophageal motility disorders.1 The Chicago classification (CC), first published in 2009, defines these disorders using HRM data. The CC has been revised over the years (2011, 2015, and 2022) for improved clinical relevance.2,3 The latest version, CC version 4.0 (CC v4.0), includes a manometric protocol in supine and upright positions. It introduces provocative tests like multiple rapid swallows and the rapid drink challenge (RDC) to enhance diagnostic accuracy. RDC is based on the normal response (esophageal body inhibition and lower esophageal sphincter [LES] contraction) to consecutive swallows.4 When the clinical diagnosis remains inconclusive based on HRM data, CC v4.0 recommends using additional tests, such as a timed barium test or a functional luminal imaging probe (FLIP).5 However, diagnostic yield and clinical cutoff value of RDC of tools produced by various manufacturers are yet to be standardized. This study investigated the diagnostic yield of RDC and compared diagnoses under CC v3.0 and CC v4.0, considering the cutoff value estimated using FLIP.

Materials and Methods

Study Sample

A total of 570 patients who underwent esophageal manometry with RDC at Asan Medical Center between January 2019 and October 2022 were enrolled in the study. Patients who failed RDC (n = 99) and those who underwent peroral endoscopic myotomy or balloon dilatation (n = 18) were excluded (Fig. 1). Informed consent was obtained from all subjects before the examination, and the study was approved by the institutional review board of Asan Medical Center and was conducted following the Declaration of Helsinki guidelines (Approval No. 2022-1678).

Figure 1. Study flow. POEM, peroral endoscopic myotomy; RDC, rapid drink challenge; EGJOO, esophagogastric junction outflow obstruction; IEM, ineffective esophageal motility.

Esophageal High-resolution Manometry

Esophageal HRM was conducted following the standard HRM protocol of CC v4.0.4 Patients fasted for at least 4 hours before the HRM procedure. After positioning the HRM catheter and capturing a 30-second baseline period, the patients swallowed 5 mL of normal saline 10 times in the supine position and 5 mL of normal saline 5 times in the upright position. Additional provocative tests were also performed. For the RDC, subjects were instructed to ingest 200 mL of normal saline through a straw as quickly as possible. The integrated relaxation pressure (IRP) of each test was measured using devices manufactured by Diversatek Healthcare. The normal values for IRP in the supine and upright positions were 22 mmHg and 15 mmHg, respectively. HRM data were analyzed using the Zvu Advanced GI Diagnostic Software (Diversatek Healthcare, Highlands Ranch, CO, USA) by a single investigator (K.W.J).

Functional Luminal Imaging Probe

FLIP is a method used to assess the distensibility of the esophagus by measuring luminal dimensions and pressure under controlled volumetric distension. In this study, Endofli (Medtronic, Fridley, MN, USA) was employed to measure esophageal cross-sectional area, diameter, and distensibility using impedance planimetry technology. A balloon-tipped catheter with electrodes was placed transorally during a sedated upper endoscopy and positioned beyond the esophagogastric junction. Cross-sectional areas and intra-balloon pressures were measured when the balloon was distended to a volume of 70 mL. The distensibility index was calculated using the Endoflip version 2.0 impedance planimetry system procedure with Flip topography.6,7

Statistical Methods

Continuous variables were presented as medians (interquartile range). The chi-square test was used to compare motility disorder diagnoses between CC v3.0 and CC v4.0. Receiver operating characteristic (ROC) analysis based on FLIP data with a normal distensibility index > 3 mmHg/mm2 was utilized to assess the clinical cutoff value of RDC-IRP. A P-value of < 0.05 was considered statistically significant. All statistical analyses were conducted using R software version 4.1.0.

Results

Patient Characteristics

Table 1 shows the baseline characteristics of the 453 patients included in our study. The median age was 61 (interquartile range, 50-67) years, and 58.9% (n = 267) of the participants were female. The most common reported symptom was dysphagia (n = 204, 45.0%), followed by epigastric/chest pain (n = 75, 16.6%), dyspepsia (n = 53, 11.7%), and globus (n = 49, 10.8%).

Table 1 . Baseline Characteristics

Variablesn = 453
Age (yr)61 (50-67)
Sex
Male186 (41.1%)
Female267 (58.9%)
Symptoms
Dysphagia204 (45.0%)
Epigastric pain75 (16.6%)
Dyspepsia53 (11.7%)
Globus49 (10.8%)
Heartburn45 (9.9%)
Nausea/vomiting10 (2.2%)
Sore throat13 (2.9%)
Cough3 (0.7%)
Voice change1 (0.2%)

Data are expressed as the median (interquartile range) or n (%).



Subgroup Analysis of Patients Who Failed Rapid Drink Challenge

Among the 570 patients, 99 failed RDC (Fig. 1). The RDC failure group consisted of 38 patients with achalasia, 11 with esophagogastric junction outflow obstruction (EGJOO), 7 with ineffective esophageal motility, 1 with hypercontractile esophagus, and 42 with normalcy. Table 2 compares the results between the RDC failure and success groups. Compared to the RDC success group, the RDC failure group had a lower median age (61 years vs 42 years, P < 0.001) and a significantly higher proportion of patients with achalasia (10.4% vs 38.4%, P < 0.001). The median failure amount during RDC was 80 mL. Subgroup analysis between achalasia and non-achalasia patients in the RDC failure group showed no significant difference (Supplementary Table 1).

Table 2 . Comparison Between the Rapid Drink Challenge Failure and Rapid Drink Challenge Success Groups

VariablesRDC failed
(n = 99)
RDC succeeded
(n = 453)
P-value
Age (yr)42 (35-57)61 (50-67)< 0.001
Sex0.382
Male46 (46.5%)186 (41.1%)
Female53 (53.5%)267 (58.9%)
Achalasia< 0.001
No61 (61.6%)406 (89.6%)
Yes38 (38.4%)47 (10.4%)
Amount of failure (mL)80.0 (50.0-110.0)

Data are expressed as the median (interquartile range) or n (%).



Clinical Cutoff Value and Diagnostic Yield of Rapid Drink Challenge–Integrated Relaxation Pressure

The diagnostic cutoff value of RDC-IRP was estimated using ROC analysis based on FLIP data from 92 patients (78 with achalasia, 7 with EGJOO, 4 with hypercontractile esophagus, and 3 with ineffective esophageal motility) with a normal distensibility index > 3 mmHg/mm2 (Fig. 2). The estimated cutoff value of RDC-IRP was 19 mmHg with a sensitivity of 76.4% and specificity of 65.0%, yielding an area under the curve of 0.772 and a predictive value < 0.001.

Figure 2. Rapid drink challenge–integrated relaxation pressure (RDC-IRP) driven by functional luminal imaging probe (FLIP) data on receiver operating characteristic (ROC) analysis. AUC, area under the curve.

A diagnostic flowchart was constructed according to CC v4.0, utilizing the cutoff value of RDC-IRP derived from FLIP data (Fig. 3). Of the 453 participants, 50 and 86 were diagnosed with achalasia and EGJOO, respectively. Among the 127 patients with abnormal supine and upright IRP, 55.1% (n = 75) had an RDC-IRP > 19 mmHg. Among the 309 patients with either abnormal supine or upright IRP, 9 had their diagnosis changed after undergoing RDC. Six patients had an RDC-IRP > 19 mmHg, and 3 displayed pan-esophageal pressurization during RDC. Figure 4 illustrates the HRM results of a 61-year-old male whose diagnosis was altered by RDC. Esophagogastric junction relaxation was observed during swallowing, while pan-esophageal pressurization was noted during RDC. This patient was eventually diagnosed with achalasia based on FLIP data.

Figure 3. Diagnostic flowchart plotted according to Chicago classification version 4.0 using the rapid drink challenge–integrated relaxation pressure (RDC-IRP) cutoff value determined using functional luminal imaging probe (FLIP) data. POEM, peroral endoscopic myotomy; EGJOO, esophagogastric junction outflow obstruction; IEM, ineffective esophageal motility.
Figure 4. High-resolution manometry result of 61-year-old whose diagnosis was changed by rapid drink challenge.

Comparison of Diagnosis Between Chicago Classification Version 3.0 and 4.0

Supplementary Table 2 presents a diagnostic comparison between CC v3.0 and CC v4.0. Diagnoses were consistent in 58.1% (n = 263) of cases. However, in 41.9% (n = 190) of cases, there was a shift to a new diagnosis under CC v4.0. Supplementary Figure illustrates the proportion of esophageal motility disorders diagnosed by CC v3.0 and CC v4.0. The changes in diagnosis from CC v3.0 to CC v4.0 were primarily influenced by shifts in the proportion of EGJOO diagnoses. Among the 249 patients previously diagnosed with EGJOO according to CC v3.0, 121 subjects (48.6%) were reclassified as normal under CC v4.0.

Discussion

In our study, the diagnostic cutoff value of RDC-IRP, derived from ROC analysis using HRM and Endoflip data, was found to be 19 mmHg. Among the 552 patients, 99 failed RDC. The RDC failure group included significantly younger patients (42 years vs 61 years, P < 0.001) and a significantly higher proportion of achalasia patients (38.4% vs 10.4%, P < 0.001). According to our results, the implementation of CC v4.0 increased the diagnostic yield by 2.0% with the addition of RDC (9 out of 453 patients). Although HRM is a standard modality for evaluating esophageal motor function, it has several limitations. One of these limitations is that its results cannot accurately reflect actual swallows in real life as it evaluates pressure and bolus transit of the esophagus using single water swallows in the supine position. To overcome this limitation, CC v4.0 introduced RDC as a provocative test. During RDC, esophageal body contraction is suppressed, which induces complete relaxation of the LES through central and peripheral deglutitive inhibition. Augmented peristalsis and LES contraction can be observed after the final swallow during RDC. This test enables the evaluation of the volume factor associated with swallowing.5,8 Although previous studies have emphasized the role of RDC during the diagnostic process, our study initially focused on the actual additional diagnostic yield of RDC by adding it to the diagnostic hierarchy.

The estimated cutoff of RDC-IRP, determined through ROC analysis, was found to be 19 mmHg. We used devices manufactured by Diversatek for HRM measurements. The cutoff value of RDC-IRP in devices manufactured by Medtronics is 12 mmHg.9 A comparison of the supine and upright IRP values from each manufacturer revealed that the set points of IRP in Medtronics devices were lower than those in Diversatek devices.10,11 This discrepancy may have been due to differences in catheter diameter and pressure sensing technology used by different companies for HRM. Furthermore, other factors, such as age or race, may also contribute to these variations.9,11 A previous study that suggested a normal IRP value of 12 mmHg was based on asymptomatic healthy controls with a mean age of 30 years.9 However, the mean age in our study was significantly higher at 57.6 years. Age is one of the factors that can influence the results of manometry tests.12,13 Nevertheless, further studies may be necessary to delve deeper into these differences and explore their clinical implications.

In this study, RDC had a failure rate of 17.9% (99 out of 552 patients). Among the failure group, 57.6% had major motility disorders, while 42.3% were found to be normal. It can be assumed that performing RDC may be challenging for both patients with and without major motility disorders. According to CC v4.0, RDC is essential in the diagnostic hierarchy for all cases. However, considering the significantly higher proportion of achalasia patients in the RDC failure group, RDC must be performed in patients who exhibit definite manometric features during 5-mL swallows in either the supine or upright positions to diagnose motility disorders.

Upon comparing the diagnosis between CC v3.0 and CC v4.0, 41.9% (n = 190) of cases had a change in diagnosis, primarily due to a shift from EGJOO to normalcy. In addition, when examining the diagram of diagnostic proportions, there was an increased proportion of achalasia and normalcy cases and a decreased proportion of EGJOO cases. Applying CC v4.0 may help narrow the diagnostic gray zone and improve diagnostic accuracy.

CC v4.0 led to a 2.0% increase in the diagnostic yield of RDC, benefiting 9/453 patients. However, it is important to note that RDC had a relatively high failure rate of 17.9%, affecting 99 out of 552 patients. Considering the relatively low diagnostic yield and substantial RDC failure rate, we suggest adopting an individualized manometric approach.

Financial support

None.

Conflicts of interest

None.

Author contributions

Conceptualization: Kee Wook Jung; formal analysis: Hoyoung Wang; investigation: Jin Hee Noh, Hee Kyoung Na, Ji Yong Ahn, Kee Wook Jung, Jeong Hoon Lee, Do Hoon Kim, Kee Don Choi, Ho June Song, Gin Hyug Lee, and Hwoon-Yong Jung; writing-original draft: Hoyoung Wang; and writing review and editing: Kee Wook Jung. All authors revised and approved the final version of the manuscript.

Supplementary Materials

Note: To access the supplementary tables and figure mentioned in this article, visit the online version of Journal of Neurogastroenterology and Motility at http://www.jnmjournal.org/, and at https://doi.org/10.5056/jnm23149.

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