Correlation Between Peak Upper Esophageal Sphincter and Pharyngeal Pressures in Patients With Dysphagia

Abstract

ABSTRACT

Objective

The upper esophageal sphincter (UES) serves multiple functions in the management of the upper aerodigestive tract. Prior investigations have defined the roles of UES resting and nadir pressures in normal swallowing. The distinctly high‐amplitude UES peak pressures, a patterned feature of pressure propagation in the transition from the pharynx to the esophagus on high‐resolution manometry (HRM), have not been characterized beyond normative data reports. This study investigated the relationship between peak UES and pharyngeal pressures at the velopharyngeal and tongue base regions in both patients with dysphagia and healthy controls.

Methods

Sixty‐three adult patients with dysphagia underwent pharyngeal HRM to obtain peak measures of velopharyngeal, tongue base region, and UES pressures. Age‐ and sex‐matched healthy controls were analyzed for comparison.

Results

UES peak pressures in patients with dysphagia showed no significant correlation with velopharyngeal or tongue base region pressures (p > 0.05). In contrast, UES peak pressures were positively correlated with velopharyngeal (r = 0.525, p < 0.001) and tongue base (r = 0.415, p = 0.001) region peak pressures in healthy subjects. Velopharyngeal region pressures showed a significant correlation with tongue base region pressures in both patients with dysphagia (r = 0.377, p = 0.002) and healthy subjects (r = 0.406, p = 0.001).

Conclusions

Pharyngeal and UES peak pressures are correlated in healthy subjects; loss of this relationship in patients with dysphagia indicates that UES peak pressures may be influenced by factors independent of pharyngeal contractile responses and bolus‐related sensory feedback.

Level of Evidence

4.

Introduction

The upper esophageal sphincter (UES) ministers to both the upper aerodigestive tract and the esophagus, regulating esophageal bolus entry while protecting the airway from gastric or esophageal contents. Functions of the UES in swallowing have been defined by manometric events, namely, resting pressures between swallows, nadir pressures during swallows, and peak UES pressures immediately following the nadir pressure [1]. UES peak pressure represents a distinctly high-pressure event immediately following UES opening that results from both muscular contraction and concurrent downward movement of the UES against the bolus tail [2, 3]. UES peak pressures have shown a strong correlation with electromyography (EMG) measures of cricopharyngeal muscle activity [4].

The purpose that UES peak pressures serve in swallowing function has not yet been defined. High amplitude UES pressure peaks have been quantified in normative studies, with pressures ranging from 192 to 306 mmHg [3–6]. Protective UES contraction in response to esophageal events or increased intrathoracic pressure has been well established in humans [7–13]. Reflexive cricopharyngeal contraction, presumed to maintain active UES closure in the event that esophageal contents approach the upper airways, has been characterized by mean peak pressures ranging from 32 to 164 mmHg, in response to phonation tasks, esophageal air and water injection, and soft cough [8, 9, 12, 13]. It is only upon hard cough that cricopharyngeal pressures exceed 200 mmHg [8]. Mean UES peak pressures in healthy young adults have been measured as commensurate with tongue base region mean peak pressures that serve bolus transit, the latter ranging from 251 to 337 mmHg dependent on bolus volume [3]. The uniquely high amplitudes of UES peak pressures in the transition between pharyngeal and proximal esophageal pressure propagation prompted questions about whether UES peak pressures may be generated in continuity with pharyngeal pressures just superior to this region to facilitate bolus transit into the esophagus.

When considering how disease may impact UES peak pressures as it does pharyngeal pressures, evidence is sparse. A small study evaluating pharyngeal manometric pressures in 11 patients with neuromuscular disease described UES peak pressures that were significantly lower than those of healthy, age-matched controls [14]. Cricopharyngeal EMG studies that included individuals with dysphagia of neurogenic etiology verified reduced cricopharyngeal recruitment associated with vagal nerve injury and central nervous system pathology [15]. The nature of the relationship between pharyngeal and UES pressures in both healthy adults and those with dysphagia remains unclear and has not been previously investigated. This study tested the hypothesis that UES peak pressures are positively correlated with velopharyngeal and tongue base regional peak pressures as measured with pharyngeal high-resolution manometry (HRM) in both patients with dysphagia and healthy, age- and sex-matched controls.

Methods

Participants

The University of Wisconsin Madison Voice and Swallow Outcomes Database was used to conduct this study. Establishment and subsequent use of the database has been approved by the University of Wisconsin—Madison School of Medicine and Public Health Institutional Review Board. Patient consent was obtained for those visiting the Otolaryngology Head and Neck Clinic for complaints related to voice and swallow. The database included patient health information for over 5000 persons.

Patients who were 18 years of age or older were identified in the database as having undergone pharyngeal HRM as part of their clinical care to address complaints of dysphagia. All pharyngeal dysphagia etiologies were included in this study. Patients who were evaluated with 10 mL bolus volumes were included. Demographic variables retrieved from the database for eligible subjects included age, sex, and dysphagia severity.

Age- and sex-matched controls were selected from a normative HRM database, previously approved by the University of Wisconsin—Madison School of Medicine and Public Health Institutional Review Board. Healthy control participants gave consent prior to participation and had no known history of neurological, gastrointestinal, or respiratory disorders.

Data Extraction

Data were extracted for patients over the age of 18 who underwent pharyngeal HRM as part of standard dysphagia care during the period of January 2012 to June 2016. All data were collected in an upright position using a solid-state high-resolution manometry system (ManoScanZ HRM System, Sierra Scientific Instruments). Pharyngeal HRM studies in patients with dysphagia were administered by trained speech-language pathologists at the University of Wisconsin-Madison (UW) Voice and Swallow Clinics in accordance with institution policies for peer-reviewed competence. Peak pressure values for velopharyngeal, tongue base, and UES were extracted from the database for 10 mL saline bolus swallow tasks. Pressure values were derived from manual selection of regions of interest as previously described [4], and values were then averaged over three trials. Dysphagia severity ratings were also extracted, characterized by a seven-point dysphagia severity rating scale based upon the American Speech-Language Hearing (ASHA) Functional Communication Measure for Swallowing [16].

Data for age- and sex-matched healthy controls were extracted from the normative HRM database for 10 mL volumes of saline averaged over five trials. All pharyngeal HRM data collected for the database were obtained using a solid-state HRM system (ManoScanZ HRM System, Sierra Scientific Instruments). HRM peak measures for velopharyngeal, tongue base, and UES regions were derived using an automated HRM analysis program described previously [17, 18].

Statistical Analysis

Statistical analyses were performed using IBM SPSS Statistics version 23 and SAS/STAT software, version 9.4, copyright 2013 SAS Institute Inc. (Cary, NC, USA). Group medians for HRM measures in each pressure region were compared using Mann–Whitney U-tests for the velopharyngeal and tongue base regions, and the Kolmogorov–Smirnov test for UES peak pressure. Spearman's rank-order correlations were calculated to determine the relationship between peak velopharyngeal region, tongue base region, and UES measures for both patients with dysphagia and healthy participants. An alpha-criterion of p ≤ 0.05 was used to determine statistical significance.

Results

Data were extracted for sixty-three patients who met inclusion and exclusion criteria for the dysphagia group, including a total of 36 males and 27 females. Patients ranged in age from 23 to 91 years, with a mean age of 65 ± 16 years. Patient demographics, as well as dysphagia severity ratings and medical diagnoses, can be found in Table 1. Thirty-five percent of patients had mild–moderate dysphagia, representing the mode of the sample. Dysphagia etiology was highly varied, with Zenker's diverticulum comprising the largest proportion of patients at 14%. Healthy controls were age- and sex-matched to patients and extracted from the normative HRM database. Healthy controls ranged in age from 23 to 89 years, with a mean age of 63 ± 16 years.

TABLE 1 Dysphagia group demographics.

	Number (%) patients n = 63
Sex
Male	38 (60%)
Female	25 (40%)
Mean age (SD): 66 years (15)
< 70 years	34 (54%)
≥ 70 years	29 (46%)
Dysphagia severity
Functional	8 (13%)
Minimal	2 (3%)
Mild	13 (21%)
Mild–moderate	22 (35%)
Moderate	8 (13%)
Moderate–severe	3 (5%)
Severe	3 (5%)
Dysphagia diagnosis
Unknown	13 (20%)
Zenker's diverticulum	9 (14%)
Head and neck cancer	6 (10%)
Other	6 (10%)
Reflux	5 (8%)
Head and neck surgery	4 (6%)
Cricopharyngeal dysfunction	4 (6%)
Cricopharyngeal myotomy	4 (6%)
Stroke	3 (5%)
Cardiac surgery	3 (5%)
Esophageal stricture	2 (3%)
Post-polio syndrome	2 (3%)
Parkinson disease	1 (2%)
Muscular dystrophy	1 (2%)

Median HRM peak measures and analysis of differences for the velopharyngeal region, tongue base region, and UES in patients with dysphagia and healthy controls are depicted in Figure 1. No significant differences were found in HRM peak measures for the velopharyngeal (median difference 11 mmHg, p = 0.27) and tongue base regions (median difference 6.3 mmHg, p = 0.70). A significant difference was found in UES peak pressures between groups, with the patient group showing significantly higher measures than healthy controls (median difference 29 mmHg, p = 0.002). Correlations were analyzed among the three regions by group (Table 2). In patients with dysphagia, velopharyngeal and tongue base region pressures were positively correlated (r = 0.377, p = 0.002). However, no significant relationships between UES peak pressures and velopharyngeal pressures (r = 0.232, p = 0.068) and tongue base region pressures (r = 0.229, p = 0.071) were identified. Healthy controls showed significant correlations among the three regions (p ≤ 0.001).

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TABLE 2 Correlations among velopharyngeal region, tongue base region, and UES peak pressures in healthy controls and patients with dysphagia.

	Healthy controls	Patients with dysphagia
Velopharyngeal region	Tongue base region	Velopharyngeal region	Tongue base region
Rho	p	Rho	p	Rho	p	Rho	p
Velopharyngeal region	1.000	—	0.406	0.001a	1.000	—	0.377	0.002a
Tongue base region	0.406	0.001a	1.00	—	0.377	0.002a	1.000	—
UES	0.525	< 0.001a	0.415	0.001a	0.232	0.068	0.229	0.071

Comparison of differences in median peak pressures between patients with dysphagia and healthy controls is listed in Table 3. A significantly higher median UES peak pressure was evident in the patient group (p = 0.002). In contrast, no significant differences were found between median velopharyngeal region (p = 0.27) or tongue base region (p = 0.70) peak pressures.

TABLE 3 Median peak pressure differences between patients with dysphagia and healthy controls.^a

	Median (IQR)	Test completed	Test statistic value	p
Healthy controls	Patient group	Difference between groups
Nasopharyngeal region	170 (126, 205)	181 (132, 233)	−11	Mann–Whitney U test	z = −1.09	0.27
Tongue base region	132 (108, 163)	126 (95, 190)	6	Mann–Whitney U test	z = 0.39	0.70
UES peak	232 (184, 258)	261 (181, 346)	−29	Kolmogorov–Smirnov	D = 0.33	0.002a

Data for each peak measure relationship were plotted for both patient and healthy control groups, illustrating the loss of the relationship among UES and pharyngeal pressures exhibited by patients with dysphagia (Figure 2). Graphs were then replotted with patients labeled by dysphagia etiology (Figure 3). Clusters of outliers were not explained by any shared dysphagia etiology.

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Discussion

In this study, neither velopharyngeal nor tongue base region peak pressures were correlated with UES peak pressures in patients with dysphagia, though all three pressures were correlated in healthy subjects. At the same time, study results substantiated a moderate relationship between velopharynx and tongue base region peak pressures regardless of health status.

The loss of correlation between pharyngeal and UES peak pressures in the patient group suggests a decoupling of neurologic regulation between the pharynx and UES. Interestingly, no specific pathology appeared to account for the clusters of patients with dysphagia who exhibited this dissociation. A previous EMG study of the cricopharyngeus in anesthetized and awake canines showed resting tone in the awake state was eliminated under anesthesia, while peak pressures during reflexive swallows remained equivalent to the awake state, suggesting that cricopharyngeal control is under multiple influences beyond the medullary central pattern generator for swallowing to serve additional roles in respiratory and airway protective functions [19]. Future study of larger patient samples may allow more robust examination of etiology subgroups and factors beyond pharyngeal contractile pressures.

UES peak pressures in patients with dysphagia were noted to be significantly higher than those of healthy controls (Figure 1). Composition of the cricopharyngeus may contribute to a specialized capability for high peak pressures. Canine studies have suggested that muscular and connective tissue in the cricopharyngeus may account for both basal tone and contractile properties during swallowing [19]. Cadaver studies of the human cricopharyngeus have reported similar composition [20], implicating unique tissue properties capable of high-magnitude pressures. Recent research examining healthy UES peak pressure responses to changes in bolus volume and viscosity found no significant pressure differences post-swallow among 5-, 10-, and 20-mL volumes or between IDDSI level 0 and 4 viscosities [21]. However, UES peak pressure was shown to diminish between the first and second presentations of equivalent viscosity volumes over time, reflective of complex sensorimotor responses [21]. Further study is needed to understand the full array of factors that influence UES peak pressures in healthy swallowing in order to recognize vulnerability or compensatory capability in swallowing disorders. High amplitudes of UES peak pressures could serve functions beyond bolus containment in the esophagus. This database study's sample of patients with dysphagia was skewed toward milder dysphagia severity, and it would be important to examine UES peak pressures in more severe dysphagia with homogeneous etiologies.

Limitations of this study include the focus on UES peak pressure, which is comprised of maximum measures at a single time point and cannot reflect pharyngeal and UES pressures over time. Additional analysis of UES manometric measures, using more sophisticated measures of hypopharyngeal intrabolus pressures and flow metrics, may better describe profiles of swallowing dysfunction by representing UES events over the course of bolus transit [22]. Additionally, correlation of UES peak pressures with bolus movement on imaging studies may allow for further investigation of the clinical implications of UES pathology on swallowing function. This study used database extraction of 10 mL volumes to match an available healthy normative dataset, which may systematically exclude patients with severe to profound dysphagia who could not safely tolerate larger bolus volumes.

The inability to judge UES peak pressures on imaging studies may represent a meaningful gap in fully capturing UES state and contributions during swallowing. This preliminary study suggests that UES neural inputs may be more complex than currently realized and relatively isolated from adjacent pharyngeal functions. Further investigation of the vulnerability and consequences of these poorly understood swallowing pressures may inform diagnostic and treatment practices in dysphagia care.

Acknowledgments

The authors would like to thank Xing Wang and Dou-Yan Yang for their statistical assistance.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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