Study on the function of pharynx & upper esophageal sphincter in globus hystericus

Abstract

AIM: Globus pharyngeus is not an uncommon symptom. Presently, its unclear dated pathophysiology remains unclear and the disease can not be evaluated correctly with routine diagnostic methods. The objective of this study is to establish the normal values of pharyngeal and UES pressure, pharyngeal transit time in healthy volunteers and to compare the differences between healthy volunteers and patients with globus pharyngeus.

METHODS: Twenty-four healthy volunteers and thirty-two patients clinically diagnosed as globus pharyngeus entered the study. Pressures of pharynx and UES were measured. Pharyngeal transit time was measured by videofluoroscopic procedure.

RESULTS: Normal pressure of pharynx, and normal resting pressure of UES were 157.81 ± 63.86 mm Hg and 68.33 ± 37.56 mm Hg, respectively. The corresponding values in the patients were 175.50 ± 93.47 mm Hg and 71.38 ± 41.42 mm Hg. The pharyngeal transit time was 1.44 ± 0.30 s in normal control group, among them there were 4 cases with stasis of barium in the valleculae and one in the piriform sinus. No laryngeal penetration or aspiration was found. In the patient group, the pharyngeal transit time was 1.37 ± 0.41 s, among them there were 6 cases with stasis of barium in the valleculae and 5 in the piriform sinus. Nine cases had laryngeal penetration and 2 had aspiration. There were no statistical differences of pressures of pharynx, UES and the pharyngeal transit time between the two groups. But there was an association between laryngeal penetration and globus pharyngeus

CONCLUSION: Radiographic examination of the pharynx show specific findings of pharyngeal dysfunction in patients with globus pharyngeus. UES pressure is normal in most patients. Hence, we find no role for UES hypertonicity as an etiologic factor in globus pharyngeus.

Key Words: $[Keywords]

INTRODUCTION

Globus sensation (globus pharyngitis, globus pharyngeus) is best described as a constant sensation of something stuck or a lump or tightness in the throat. Typically, a lump, or crumb-like (foreign body) sensation, a constriction or choking[1-3] is complained. Nearly half of the general population has had intermittent symptoms resembling globus[4-6]. More severe and distressing symptoms comprise up to 4% of referrals to otolaryngological specialists[4]. In addition to emotional stress, mood, and personality disorders, it has been attributed to a high upper esophageal sphincter (UES) resting pressure, gastroesophageal reflux (GER)[7,8], esophageal dysmotility, hiatal hernia, kinematic pharyngeal transit time and local anatomic abnormalities[9-16]. Although the associations are diverse and broadly investigated, the etiology of globus still remains unclear[4].

The aim of our study was to investigate the association of globus pharyngeus with UES resting pressure and kinematic pharyngeal transit time.

MATERIALS AND METHODS

Study subject

Two groups of persons were studied: globus pharyngeus patients and the control group. The globus pharyngeus group comprised thirty-two consecutive patients presenting themselves to the otolaryngology and gastroenterology departments with predominant symptom of globus pharyngeus with no abnormality on examination of neck, larynx, or pharynx between December 2000 and March 2001. The diagnostic criteria of the globus sensation is in accordance with Rome II criteria: At least 12 wk, which need not be consecutive, in the preceding 12 mo of: (1) The persistent or intermittent sensation of a lump or foreign body in the throat; (2) Occurrence of the sensation between meals; (3) Absence of pathologic gastroesophageal reflux, achalasia, or other motility disorder with a recognized pathologic basis as scleroderma of the esophagas. The control group consisted of twenty-four healthy volunteers. The male: female ratio in the globus pharyngeus group was 1:1.29, as conpared with 1:1.4 in the control group. The mean age in the globus pharyngeus group was 47 ± 11 years (range: 28-73 years), as compared with 49 ± 17 years (range: 21-77 years). These differences were not significant. A single investigator examined all patients by videofluoroscopy and esophageal manometry.

Esophageal manometry

After an overnight fast, manometry was performed using a solid-state intraluminal transducer assembly (Konigsberg Instruments, Inc., Pasadena, USA). The catheter consists of a flexible tube containing four pressure microtransducers. The distal two are circumferential transducers that record the average pressure over 360^o. The circumferential transducer consists of a 4.6-mm-diameter silastic annulus enclosing a small transducer within a castor oil-filled chamber. The two proximal transducers with a single sensor oriented in one direction. The transducers, starting at the distal end, are separated by 3, 2 and 5 cm. Pressure data are collected on-line by means of a computerized motility system and analyzed using Polygram equipment and software [Synectics (Medtronics), Shoreview, Minnesoda].

Before the examination, the transducers were calibrated at 0 mm Hg and 50 mm Hg after balneum in 37 °C water 10 min. Manometry of the UES and pharynx was performed in the upright position. The catheter was passed through a nostril into the stomach. Then it was withdrawn in 1-cm increments every 20 s back into the esophagus. UES resting pressure was assessed using a station pull-through of the distal transducer with at least 15-sec intervals for stabilization between each 1-cm movement of the catheter, since the UES is somewhat reactive to the catheter movement. After identifying the high-pressure zone during this slow pull-through, at least 15-sec is allowed to elapse before measuring the resting UES pressure. Maximal stable pressure is recorded in millimeters of mercury using esophageal pressure just distal to the UES as zone baseline. Five 5-mL water (room temperature) swallows were used to assess UES relaxation, pharyngeal contraction, and UES/pharyngeal coordination. Swallows were 30 s apart. The swallows were performed with the circumferential transducer placed just proximal to the high-pressure zone of the UES to allow accurate recording of the pressure throughout the cycle of elevation of the sphincter during deglutition. Placement of the circumferential transducer proximal to the high-pressure zone of the sphincter compensates for orad movement during swallowing.

Mamometry helped clarify the specific timing of pressure events during pharyngeal contraction and UES relaxation[17].

Videofluoroscopy

Detailed sequential analysis of videofluoroscopic images recorded at 25 frames/s clarifies timing of the events that occur during pharyngeal contraction and UES opening. It clearly defines the key role of muscle contraction occuring early in the swallowing sequences that produce the elevation of the hyoid and larynx, which is an essential element in the opening of the UES[18-20].

Kinematic pharyngeal transit time is defined as the time from the first movement of the bolus, which results in a complete swallow, to the time the epiglottis returns to its initial position. The definition excludes oral preparation time and tongue movements that do not result in a complete swallow[21].

Videofluoroscopy was completed in both anteroposterior and lateral projections with 5-mL thin barium at room temperature[22-23]. To standardize the evaluations in our study, timing measurements were completed in the lateral projection.

The following data were collected by one physician evaluator: (1) quantitative kinematic pharyngeal transit times including the time of arrival of the head of the bolus reaching the level of the posterior inferior border of C₂ verterbral body (C₂L), the inferior level of the valleculae (BV), the posterior inferior border of C₄ verterbral body (C₄L), and the time at which the epiglottis returned to its original position (Em); These data points were selected to provide more easily identifiable radiologic landmarks for measurement[21,24-26]. (2) The presence or absence of vallecular or piriform pooling, and (3) the presence or absence of penetration of part of the bolus to or through the true vocal cord[27-29].

Statistical analysis

Fisher P test was used to compare patients and controls, with statistical significance set at the level of 0.05.

RESULTS

Kinematic pharyngeal transit time

The data of kinematic pharyngeal transit time from the control group and globus pharyngeus group were presented in Table 1.

Table 1 Kinematic pharyngeal transit time.

	Control group (n = 24)	Globus sensation group (n = 32)	P
C2L	0.50 ± 0.27	0.45 ± 0.33	> 0.05
BV	0.57 ± 0.26	0.51 ± 0.34	> 0.05
C4L	0.67 ± 0.27	0.63 ± 0.36	> 0.05
EM	1.44 ± 0.30	1.37 ± 0.41	> 0.05

Note: Times are given in seconds.

There was no statistically significant difference between the control group and globus pharyngeus group, which showed^aP > 0.05. There were four cases of volunteers presenting stasis of barium in the valleculae and one in the piriform sinus. No laryngeal penetration and aspiration were found. Meanwhile, there were six and five of patients representing stasis of barium in the valleculae and piriform sinus respectively. Nine and two of patients had laryngeal penetration and aspiration. The results of valleculae and piriform sinus stasis and airway aspiration had no statistically significant differences between the two groups. But there was an association between laryngeal penetration and globus pharyngeus.

Esophageal manometry

The data of esophageal manometry from the control group and globus pharyngeus group were presented in Table 2.

Table 2 Data of esophageal mamometry.

	Control group (n = 24)	Globus pharyngeus group (n = 32)
UES
Resting pressure	68.33 ± 37.56 mm Hg	71.38 ± 41.42 mm Hg
Residual pressure	-7.30 ± 6.48 mm Hg	-11.04 ± 6.90 mm Hg
Relaxation time (from the beginning of relaxation to the nadir)	0.27 ± 0.06 s	0.28 ± 0.15 s
Duration (time from beginning of relaxation to the end)	0.54 ± 0.08 s	0.59 ± 0.15 s
Recovery (time from nadir of relaxation to the end)	0.27 ± 0.08 s	0.33 ± 0.15 s
Pharynx
Peak pressure	157.81 ± 63.86 mm Hg	175.50 ± 93.47 mm Hg
contraction time (from the beginning of contraction to the nadir)	0.20 ± 0.06 s	0.22 ± 0.08 s
duration (time from beginning of contraction to the end)	0.42 ± 0.08 s	0.44 ± 0.12 s
Recovery (time from peak of contraction to the end)	0.22 ± 0.05 s	0.22 ± 0.06 s

There was no significant difference between the two groups (P > 0.05). And also no difference in gender in the two groups (Table 3)

Table 3 Data of male and female in two groups.

	Control group		Globus pharyngeus group
	Male	Female	Male	Female
UES resting pressure (mm Hg)	65.55 ± 34.02	70.32 ± 38.49	67.61 ± 34.39	73.65 ± 44.00
UES residual pressure (mm Hg)	-9.33 ± 6.80	-5.84 ± 5.82	-8.80 ± 6.98	-12.39 ± 6.49
Pharyngeal peak pressure (mm Hg)	165.72 ± 69.19	151.45 ± 57.36	163.19 ± 105.47	182.89 ± 81.99

DISCUSSION

Globus pharyngeus is a common disorder, accounting for 3%-10% of otolaryngologic outpatient referrals[1,4]. The cause is unknown, and is likely to be of multifactorial origin. Abnormal function of the upper esophageal sphincter (UES) may produce the globus sensation symptom[14,30]. Disorders of the UES include the hypertonsic and hypotonsic sphincter and various abnormalities of relaxation. Globus sensation has been associated with hypertonsic upper esophageal sphincter and a persistent cricopharyngeal impression (i.e., bar), and Zenker diverticulum may be seen in patients with abnormal sphincter relaxation[9-13,30-31].

Hypertonicity of the UES was suggested as an etiologic factor in the genesis of globus sensation by Watson and Sullivan[32] in a study involving only nine patients suggested hypertonicity of the UES as an etiologic factor in the genesis of globus pharyngeus. This observation was in contradiction with a previous controlled study by Calderelli et al[33], who found normal UES pressures in their patients with globus sensation. The techniques used for UES manometry in both studies might have questionable accuracy, as they did not count for the radial asymmetry of the UES pressure profile. In a more recent study, Cook et al[34] failed to demonstrate any difference in resting UES pressure between normal controls and those with a history of globus sensation. Our study, using computerized solid-state manometry with a circumferentially recording transducer has not shown increased prevalence of UES hypertonicity in patients with globus sensation.

Through studies using multi-lumen catheters, radial asymmetry of the UES has been demonstrated over a number of years[35,36]. Pressures recorded in the anterior and posterior directions were usually two or three times greater than pressures recorded laterally. This was believed to result from the anatomical disposition of the cricopharyngeus, but might be due in some extent to the compressive effect of the posterior lamina of the cricoid cartilage against the vertebral bodies of the cervical spine. So we believe that values for UES pressure are best obtained using a circumferential sensing solid-state transducer[37]. In addition to radial asymmetry, oral movement of the sphincter during deglutition complicates the manometric assessment of the UES. With the transducer located in the sphincter high-pressure zone, a recording artifact will usually occur. As the swallow is initiated, the sphincter moves oral, leaving the transducer recording esophageal pressure. This fall in pressure may be erroneously interpreted as sphincter relaxation. If, however, the transducer is located proximal to the high pressure zone, when the subject swallows and the larynx elevates, the UES (which has not yet relaxed) moves onto the transducer, which then records a rise in pressure followed by a fall in pressure as the sphincter relaxes. The pressure rises again as the sphincter regains tone and falls as the larynx returns to its original position, moving the sphincter distal to the transducer. The manometric recording in the UES that results from this sequence of events resembles the letter 'M' and this configuration can be used to ascertain correct transducer placement[38-41].

The manometric findings in our study did not demonstrate any possible origin for the globus sensation. Detailed sequential analyses of videofluoroscopic images recorded at 25 frames/s have clarified timing of the events that occur during pharyngeal contraction and UES opening[42,43]. These studies have clearly defined the key role of muscle contractions occurring early in the swallowing sequence that produce the elevation of the hyoid and larynx which is an essential element in the opening of the UES[44,45]. Videofluoroscopy was completed in both anteroposterior and lateral projections with 5 mL 250% barium sulfate liquid[27].

The initiating event in our kinemic times is approximately at the beginning of the oropharynx. Consequently, BV in our study represents transit time through the oropharynx and mesopharynx. Pharyngeal dysfunction was defined as the presence of one or more of the following findings: (1) poor laryngeal elevation and epiglottic motion; (2) laryngeal penetration or aspiration, and (3) stasis of barium in the vallecula and piriform sinuses[46,47].

Radiographic evidence of pharyngeal dysfunction such as stasis and aspiration was seen in patients, but these findings were not specific for upper esophageal sphincter dysfunction. Batch and Wilson et al[48-50] also found that pharyngeal abnormalities were rarely seen at radiography in patients with globus pharyngeus. Thus, radiographic findings suggestive of upper esophageal sphincter dysfunction were rarely present in patients with globus sensation[30].

In conclusion, findings by radiographic examination of the pharynx may show specific findings of pharyngeal dysfunction in patients with globus pharyngeus. Results of the pressures of the UES are normal in most patients with this symptom. So we find no role for UES hypertonicity as an etiologic factor for globus, but a strong association between laryngeal penetration and globus pharyngeus.