Abnormal Esophageal Distension Profiles in Patients With Functional Dysphagia: A Possible Mechanism of Dysphagia

Dysphagia is common in the general population. Many patients with dysphagia have normal endoscopy, barium swallow, and esophageal manometry findings. Rome classification classifies these patients into the category of functional dysphagia (FD).¹ Each swallow induces a wave of esophageal inhibition/distension followed by contraction, both of which travel from the top to the bottom of the esophagus in a sequential or peristaltic fashion.^2,3 High-resolution esophageal manometry (HRM) and the Chicago classification assess only the contraction phase of peristalsis. Whether patients with FD have abnormalities of the esophageal distension is not known. Intraluminal esophageal impedance of the HRM impedance (HRMZ) recordings can measure esophageal distension during peristalsis. The goal of our study was to compare the distension-contraction profile of patients with FD and control individuals.

Methods

Thirty patients with FD (18 men; mean age, 36 years; range, 21–74 years) and 33 healthy individuals (12 men; mean age, 33 years; range, 24–62) were studied. Patients were referred to the esophageal motility laboratory of the University of California San Diego following normal upper endoscopy, esophageal biopsy, and routine HRM study findings. The human investigation committee of the University of California San Diego approved the study (institutional review board no. 182156).

All participants completed the Brief Esophageal Dysphagia Scoring questionnaire, and patients with score of >10 (range, 10–25) were included in the study. Recordings were performed by using an HRMZ catheter (Medtronic Inc). After topical anesthesia and placement of the HRMZ catheter, 8 to 10 swallows of 10 mL 0.5-N saline warmed to 37°C were recorded with the participants in the Trendelenburg position (−15°). In another 12 patients with FD and 10 control individuals, synchronized HRMZ and ultrasound images of the esophagus at 6 cm above the lower esophageal sphincter (LES) were recorded.

The HRMZ recordings were analyzed by using a MATLAB-based program (Dplots, Motilityviz), which extracted following parameters from 4 esophageal segments, 1 and 4 being proximal and distal, respectively: (1) peak amplitude and area under the curve (AUC) of distension, (2) peak amplitude and AUC of contraction, (3) time period between the onset of upper esophageal sphincter relaxation and peak distension (nadir impedance) (T1), and (4) time between T1 and peak contraction (T2). A composite image of the M-mode ultrasound image and distension-contraction plots was built for 3 representative swallows in each participant. A B-mode US image at the instance of nadir impedance was extracted, and luminal cross-sectional area (CSA) was measured with National Institutes of Health ImageJ analysis software.

Data are reported as median (interquartile range), unless otherwise stated. Across-participant comparisons were made by using a nonparametric Wilcoxon signed rank test for all comparisons and Wilcoxon rank sum test in the case of unpaired data.

Results

Although there is no difference between the HRM of a healthy individual and a patient with FD, the amplitude of luminal distension is smaller, peak distension occurs earlier (smaller T1), and distension waveform is irregular and fragmented in the patient. Esophageal distension progresses sequentially along the esophagus (shaped like an American football) in close temporal relation (ahead) with contraction in a healthy individual. In patients, the distension amplitude is smaller, and peak distension is located well ahead of contraction (Figure 1).

Figure 1.

(A, B) From left to right, impedance topographs with overlaid distension waveforms on pressure in (A) a healthy individual and (B) a patient with functional dysphagia—10-mL bolus in the Trendelenburg position. (C) A reconstructed cylindrical representation of impedance-derived distension and pressures along the length of the esophagus for both participants. Note the difference in the patterns of distension and temporal correlation between distension and contraction along the length of the esophagus in the healthy individual and the patient with FD. secs, seconds.

The peak pressure and AUC of pressure were not different between the 2 groups. On the other hand, the peak distension was different in the first and fourth segments between the 2 groups (first segment: median values of 115.23 mm² [14.23] for healthy individuals and 94.68 mm² [25.66] for patients with FD, P = .007); fourth segment: mm² 195.07 [20.74] for healthy individuals and 159.66 mm² [52.37] for patients with FD, P = .016). More significant were the differences in the AUC of distension, which was lower in patients with FD in all 4 segments (Supplementary Figure 1). T1 was smaller in patients in the fourth segment: 3.24 seconds (0.52) vs 3.94 seconds [0.93] in healthy individuals (P < .001). The receiver operating characteristic analysis showed the highest AUC for distension (0.88 for segments 1 and 4). No correlation was found between the Brief Esophageal Dysphagia Scoring score and measured parameters.

In 12 patients in whom ultrasound imaging was performed concurrently, findings showed smaller T1 and AUCs of distension and peak distension amplitude in patients, similar to those of other patients. Ultrasound image analysis showed similar muscle thickness at baseline and during the distension and contraction phases of peristalsis in the 2 groups. However, luminal CSA measured from ultrasound images at the time of nadir impedance (peak distension) was smaller in patients (166.12 mm² [8.4] vs 97.1 [48.1] mm²) (Supplementary Figure 2).

Discussion

Findings similar to ours have been reported in patients with FD,^4,5 that is, higher nadir impedance value (which implies lower luminal CSA) and alteration in the temporal relationship between distension and contraction. Lower CSA during bolus transport implies a narrower esophagus. Based on the principles of fluid flow (Poiseuille law), one would expect a greater velocity of fluid flow and faster arrival of the bolus in the distal esophagus in a narrow tube, that is, a smaller T1, which is what we found. A higher velocity of flow in patients explains why the same volume (10 mL) of swallowed bolus entering and leaving the esophagus can have a lower amplitude of distension in patients with a narrower esophagus compared to healthy individuals.

Standard HRMZ recordings use a 5-mL liquid bolus to assess esophageal peristalsis, which is not a significant challenge to test the distensibility of esophagus. With solid food challenge, many more patients have abnormal recordings than with liquid swallows.⁶ The lack of correlation between dysphagia score (subjective) and distension abnormalities (objective) may raise doubts about the cause-and-effect relationship between distension abnormalities and dysphagia symptoms. However, lack of correlation between subjective and objective findings, in general, and during HRM recordings remains a challenge.⁷ A recent study found no differences in the dysphagia scores between patients with achalasia esophagus, distal esophageal spasm, nutcracker/jackhammer esophagus, and esophagogastric junction outflow obstruction,⁸ even though one would expect higher dysphagia scores in achalasia because of the greater objective esophageal motor abnormalities (impaired LES relaxation and no peristalsis) than esophagogastric junction outflow obstruction (impaired LES relaxation with normal peristalsis).

In summary, we found bolus flow abnormalities in patients with FD, which we propose are the cause of dysphagia sensation.

Supplementary Material

Note: To access the supplementary material accompanying this article, visit the online version of Gastroenterology at www.gastrojournal.org, and at https://doi.org/10.1053/j.gastro.2020.12.002.

Abbreviations used in this paper:

AUC

area under the curve

CSA

cross-sectional area

FD

functional dysphagia

HRM

high-resolution esophageal manometry

HRMZ

high-resolution esophageal manometry impedance

LES

lower esophageal sphincter