Abstract
Oropharyngeal dysphagia due to upper esophageal sphincter (UES) dysfunction is commonly encountered in the clinical setting. Selective experimental perturbation of various components of the deglutitive apparatus can provide an opportunity to improve our understanding of the swallowing physiology and pathophysiology. The aim is to characterize the pharyngeal and UES deglutitive pressure phenomena in an experimentally induced restriction of UES opening in humans. We studied 14 volunteers without any dysphagic symptoms (7 men, 66 ± 11 yr) but with various supraesophageal reflux symptoms. To induce UES restriction, we used a handmade device that with adjustment could selectively apply 0, 20, 30, or 40 mmHg pressure perpendicularly to the cricoid cartilage. Deglutitive pharyngeal and UES pressure phenomena were determined during dry and 5- and 10-ml water swallows × 3 for each of the UES perturbations. External cricoid pressure against the UES resulted in a significant increase in hypopharyngeal intrabolus pressure and UES nadir deglutitive relaxation pressure for all tested swallowed volumes (P < 0.05). Application of external cricoid pressure increased the length of the UES high pressure zone from 2.5 ± 0.2 to 3.1 ± 0.2, 3.5 ± 0.1, and 3.7 ± 0.1 cm for 20, 30, and 40 mmHg cricoid pressure, respectively (P < 0.05). External cricoid pressure had no significant effect on pharyngeal peristalsis. On the other hand, irrespective of external cricoid pressure deglutitive velopharyngeal contractile integral progressively increased with increased swallowed volumes (P < 0.05). In conclusion, acute experimental restriction of UES opening by external cricoid pressure manifests the pressure characteristics of increased resistance to UES transsphincteric flow observed clinically without affecting the pharyngeal peristaltic contractile function.
Keywords: deglutition, manometry, pharynx, UES, pressure
dysphagia, a potentially debilitating and life-threatening condition, affects ∼16 million individuals in the United States, 30 million in Europe, and 10 million in Japan annually (7). Sixty to 80% of patients with neurological disorders such as stroke, dementia, and Parkinson's disease exhibit dysphagia (6, 11, 13, 27, 30). Common symptoms include difficulty or incomplete swallowing and aspiration of food or liquid into the lungs and often lead to malnutrition, dehydration, and aspiration pneumonia (6, 7, 13, 29). Dysphagia affects individuals of all ages but especially the elderly (13, 17, 29, 30). The total cost for dysphagia including hospitalization in the United States is estimated over $1 billion per year (30a). As such oropharyngeal dysphagia represents a significant impairment to health and quality of life of patients as well as a substantial burden to the society.
Despite these recognitions, advances in prevention, diagnosis, and therapy/management of oropharyngeal dysphagia have been unacceptably slow. Chief among reasons for this shortcoming is the inability to experimentally simulate various functional abnormalities associated with oropharyngeal dysphagia by selectively and individually perturbing various elements of the deglutitive apparatus and to study the consequences of the malfunction of each of these elements on the swallow function in general and specifically its effects on other interrelated elements.
This approach requires reducing the deglutitive apparatus involved in the pharyngeal phase of swallowing to its finite elements. Within the limitations of studies in humans, one may consider those elements that contribute to propelling the bolus such as the tongue and pharyngeal muscles; those that protect the airway such as the laryngeal structures including the vocal cords, glottis, and epiglottis as well as the soft palate and uvula; and lastly those that constitute the upper esophageal sphincter (UES), including the cricopharyngeus, inferior constrictor, and proximal esophageal muscles, which by its timely opening and closure in relation to bolus-propelling and airway-protective elements allows complete bolus transit out of the pharynx and into the esophagus. It is the latter element that is the topic of this article. Oropharyngeal dysphagia due to UES dysfunction is common and is seen following stroke (27), radiation therapy for head and neck malignancies (14, 15, 28), chronic reflux (28), and aging (13, 17, 29, 30).
For this reason in this study we aimed to selectively perturb the UES opening function and determine the effect of a set of known degrees of restrictive pressures on the pharyngeal and UES pressure phenomena.
METHODS
We studied 14 volunteers (7 men, age 66 ± 11 yr) without any swallowing difficulty or neural or neuromuscular disorders that may affect swallowing function. However, they had a variety of supraesophageal reflux symptoms including chronic cough, burning throat, hoarseness, excess phlegm, and throat clearing. All subjects were followed up by their primary gastroenterologist in a tertiary care referral center with established diagnosis of gastroesophageal reflux disease and were on long-term acid-suppressive therapy. Despite ongoing therapy, all patients complained of persistent troublesome regurgitation along with at least one of the above supraesophageal manifestations. The Medical College of Wisconsin institutional review board approved the studies and all participants signed written, informed consent prior to their studies.
High-Resolution Manometric Evaluation of the Pharynx and UES
A solid-state manometric assembly with 36 circumferential sensors spaced at 1-cm intervals (outer diameter 4.2 mm) was used (Given Imaging, Los Angeles, CA) to measure intraluminal pharyngeal and UES pressures. This device uses proprietary pressure transduction technology (TactArray) that allows each of the 36 pressure-sensing elements to detect pressure over a length of 2.5 mm in each of 12 circumferentially dispersed sectors. The sector pressures are then averaged to obtain a mean pressure measurement, making each of the 36 sensors a circumferential pressure detector with the extended frequency response characteristic of solid-state manometric systems. Before recording, the HRM transducers were calibrated at 0 and 100 mmHg pressures using externally applied pressure. The response characteristics of each sensing element were such that they could record pressure transients in excess of 6,000 mmHg/s and were accurate to within 1 mmHg of atmospheric pressure after thermal calibration correction. The data-acquisition frequency was 50 Hz for each sensor (ManoScan Data Acquisition, Given Imaging).
Study Protocol
After at least 6 h of fasting, 14 volunteers underwent transnasal placement of the manometric catheter following topical 2% lidocaine application until the tip of catheter was advanced in the distal esophagus. The catheter was then pulled back and positioned such that the entire pharynx and UES could be recorded. On average, seven to nine pressure sensors were in the pharynx depending on individual length of pharynx. After a 10-min adaptation period, participants were asked to complete three repetitive swallows of each of the following: dry swallow and water swallows of 5 ml and 10 ml during four UES restriction conditions (see below). The water boluses were administered at room temperature. The order of bolus swallows was randomized for each subject.
External Cricoid Pressure
To perturb the UES deglutitive function and to restrict its opening, we used a simple handmade device comprised of two components that could be comfortably worn around the neck: an elastic band and a cushion (5 × 3 × 2.5 cm). The cushion was placed horizontally at the center of the cricoid cartilage (Fig. 1A). By adjusting the elastic band by simply tightening or loosening the band, we selectively applied 0, 20, 30, and 40 mmHg pressures perpendicular to the cricoid cartilage, inducing equivalent resistance against UES opening. The applied external cricoid pressure was monitored in real time by using a small noncompliant inflated balloon (10 ml), which was placed between the cricoid cartilage and the cushion and was connected to a manometer. We allowed 3 mmHg fluctuations around the target pressure with respiration of the participants.
Fig. 1.
A: handmade simple compression device comprised of two components that could be comfortably worn around the neck: an elastic band and a cushion. The cushion was placed horizontally at the center of the cricoid cartilage to apply the desired perpendicularly directed pressure. B: still frame of pharyngeal and UES pressure contour plot seen in ManoView with superimposition of measurement criteria. An example of a 10-ml water swallow with 20 mmHg external cricoid pressure is shown. P2 sensor is taken to be at the point of maximum orad UES excursion, signifying the most distal part of the hypopharyngeal pressure zone; P6 sensor is considered to be at the junction of velopharynx and oro/hypopharyngeal pressure zone; and P9 sensor is considered to record from the most proximal area of the velopharyngeal pressure zone. These sensors are located during resting period at 2, 6, and 9 cm orad to the proximal margin of UES-HPZ, respectively.
Data Collection
UES parameters.
UES NADIR RELAXATION PRESSURE.
The minimal residual pressure attained during the period of UES relaxation was recorded as UES nadir pressure.
UES BASAL PRESSURE.
Basal pressure of the UES was measured by the e-sleeve function of the ManoView program of HRM assembly averaged over three normal respiratory circles.
DURATION OF UES RELAXATION.
The duration of manometrically recorded UES relaxation was defined as the time interval between the two basal pressure points surrounding the UES nadir pressure (Fig. 1B).
LENGTH OF UES-HIGH PRESSURE ZONE.
UES-high-pressure zone (HPZ) in the resting state was outlined with 20 mmHg isobaric contour and the vertical length was measured at baseline and under different external cricoid pressure conditions.
Pharyngeal parameters.
PHARYNGEAL PEAK PERISTALTIC PRESSURE.
Peak contractile pressure values were measured at the apex of the waveform at the level of individual sensor during a swallow.
DURATION OF PHARYNGEAL PERISTALTIC CONTRACTION.
This was defined as the time interval between the onset and offset of deglutition-related pressure change. The onset of the contraction was defined as the point before the main pressure rise when the increments of positive pressure change were equal to or greater than 20 mmHg per 0.1 s (10). The offset was defined as occurring at the point where the pressure returned to baseline and the increments of negative pressure change were less than 20 mmHg per 0.1 s.
PHARYNGEAL CONTRACTILE INTEGRAL.
Pharyngeal contractile integral (PhCI) is a summary measure of the vigor of pharyngeal contraction. It was calculated as mean contractile amplitude × contractile duration × pharyngeal length (mmHg·s·cm). Considering the orad movement of UES during swallowing that could be up to 2 cm, the length of the pharynx was measured for the segment spanning from the most orad sensor registering 20 mmHg pressure to the sensor located 2 cm above the upper margin of the UES at rest. The PhCI was then further divided into velopharyngeal contractile integral (CI) and CI of the oro/hypopharynx (Fig. 1B).
HYPOPHARYNGEAL INTRABOLUS PRESSURE.
Intrabolus pressure (IBP) was defined as the hydrodynamic pressure within the swallowed bolus. Average IBP was calculated as the average pressure increment up to 20 mmHg before the onset of the upstroke of pharyngeal contraction.
All pressure measurements were referenced to atmospheric pressure.
Statistical Analysis
All statistical analyses were conducted with SAS 9.3 software. The mean and standard error were calculated for all the paradigms developed above and were summarized in the ensuing graphics and tables. Data were expressed as means ± SE. Differences across volumes and external pressure were assessed by one-way ANOVA with repeated measures. To test whether there is volume- or external pressure-dependent effect, linear trend tests were performed. Tukey-Kramer test was used for post hoc multiple comparisons. Two-tailed P values <0.05 were considered statistically significant.
RESULTS
All 14 volunteers were able to swallow all tested volumes without difficulty during 0, 20, 30, and 40 mmHg external cricoid pressures. There was no swallow-related cough or change in voice in any of the volunteers.
Effect on UES Parameters
Effect on UES relaxation nadir pressure.
UES nadir pressure was positively correlated with applied external cricoid pressure at all tested bolus volumes. For instance, application of 40 mmHg external cricoid pressure resulted in a significant increase in UES nadir pressure compared with no band, from 1.9 ± 1.1 to 8.6 ± 1.1 mmHg, 5.8 ± 1.2 to 11.4 ± 1.1 mmHg, and 7.4 ± 1.0 to 12.4 ± 1.1 mmHg for dry swallow, 5 ml, and 10 ml water swallow, respectively (P < 0.05). Similar results were also found with external cricoid pressure at 20 and 30 mmHg pressures (Table 1). Consistent with a previous study (26), UES nadir relaxation pressure was positively correlated with bolus volume, in that the larger the bolus the higher the UES nadir relaxation pressure (P linear trend test < 0.05). Table 1 shows the effect of volume on UES nadir relaxation pressure commensurate with each of the tested external cricoid pressures.
Table 1.
Effect of bolus volume and external cricoid pressure on UES nadir relaxation pressure
| External Cricoid Pressure | DS | 5 ml | 10 ml |
|---|---|---|---|
| 0 mmHg | 1.9 ± 1.1 | 5.8 ± 1.2† | 7.4 ± 1.0† |
| 20 mmHg | 4.3 ± 1.1* | 9.4 ± 1.3*† | 11.1 ± 1.0*† |
| 30 mmHg | 5.3 ± 1.1* | 10.3 ± 1.2*† | 12.1 ± 1.3*† |
| 40 mmHg | 8.6 ± 1.1* | 11.4 ± 1.1*† | 12.4 ± 1.1*† |
Values are mean mmHg ± SE.
P < 0.05 compared with no external cricoid pressure at each tested bolus volume;
P < 0.05 compared with dry swallow (DS) at each tested external cricoid pressure.
Effect on duration of UES relaxation.
During no external cricoid pressure conditions did increasing bolus volume result in significantly longer UES relaxation duration for both 5- and 10-ml boluses compared with dry swallows (P < 0.05). This volume effect persisted during application of external cricoid pressures (Fig. 2). In addition to volume effect, compared with dry swallow, there was a significant cricoid pressure effect for 30 and 40 mmHg pressures. This effect reaches statistical significance for 10-ml but not 5-ml boluses.
Fig. 2.
Effect of external cricoid pressure and bolus volume on duration of UES relaxation (mean ± SE, s). Bolus volume is positively correlated with UES relaxation duration. There is a significant cricoid pressure effect for 30 and 40 mmHg pressures for 10-ml bolus. *P < 0.05 compared with no external pressure; #P < 0.05 compared with dry swallow.
Effect on length of UES-HPZ.
Application of the external cricoid pressure increased the length of the UES-HPZ from 2.5 ± 0.2 cm without the band to 3.1 ± 0.2, 3.5 ± 0.1, and 3.7 ± 0.1 cm for 20, 30, and 40 mmHg cricoid restrictive pressure, respectively (P < 0.05 at each pressure level vs. no external cricoid pressure). There was a significant linear trend between the length of UES-HPZ and the applied external cricoid pressure (R2 = 0.35, P < 0.05, Fig. 3).
Fig. 3.
Relationship between length of UES-HPZ and external cricoid pressure. It shows a positive correlation between the length of UES-HPZ and the applied external cricoid pressure. *P < 0.05 compared with no external cricoid pressure.
Pharyngeal Parameters
Effect on pharyngeal peak peristaltic pressure.
Pharyngeal peristalsis peak pressure exhibited a progressive increase from the velopharynx at P9 (9 cm proximal to UES) to a maximal at P7 (7 cm proximal to UES) and then gradually declined along the recording sites to a nadir at P4 (4 cm above UES) from where it increased progressively to P2 (2 cm proximal to the UES). This unique pressure signature resembling a tilde (∼) was preserved during swallowing all volumes as well as during application of all external cricoid pressures 20–40 mmHg. There was no significant difference in pressure values at different sites of pharyngeal pressure tilde for different volumes and different cricoid pressures (Fig. 4A).
Fig. 4.
A: effect of external cricoid pressure on pharyngeal peak peristaltic pressure (mean ± SE, mmHg). Pharyngeal peristalsis peak pressure signature resembles a tilde (∼): a progressive increase from velopharynx at P9 to a maximal at P7 and then gradually declined along the recording sites to a nadir at P4 from where it increased progressively to P2. B: effect of external cricoid pressure on pharyngeal contractile duration (mean ± SE, s). The duration of pharyngeal peristaltic contraction exhibits a dome and slope pattern: the duration of peristaltic wave in the velopharynx peaked at P7 and P8 and then progressively decreased for recording sites closer to the UES with the shortest duration at 2 cm proximal to the UES. Bolus volumes and external cricoid pressures have no effect on pharyngeal peak peristaltic pressure and pharyngeal contractile duration. DS, dry swallow.
Effect on duration of pharyngeal contraction.
The duration of pharyngeal peristaltic contraction also showed axial asymmetry in that the duration of the peristaltic wave in the velopharynx where the longest and peaked at sites 7 and 8 cm proximal to the UES. From there, the duration progressively decreased for recording sites closer to the UES with the shortest duration at 2 cm proximal to the UES (P < 0.05 for all tested volume). Volume of swallowed bolus did not affect this pattern. This dome and slope pattern of pressure change continued to persist during swallows of application of 20, 30, and 40 mmHg external cricoid pressure (Fig. 4B).
Effect on PhCI.
Application of external cricoid pressure did not affect the CI of the velopharynx or oro/hypopharynx. However, swallowing both 5-ml and 10-ml boluses at all cricoid pressure conditions significantly increased the velopharyngeal but not oro/hypopharyngeal CI compared with dry swallow (P < 0.05). The observed bolus effect on velopharyngeal CI was preserved for all cricoid pressure conditions. A significant linear trend effect of the bolus size was also observed on velopharyngeal CI (P < 0.05). This phenomenon was preserved during application of external cricoid pressure (Fig. 5).
Fig. 5.
Effect of bolus volume on pharyngeal contractile integral (CI; mmHg·s·cm). Velopharyngeal contractile integral progressively increased with increased swallowed volumes. Bolus volume has no effect on oro/hypopharyngeal contractile integral. External cricoid pressure does not affect pharyngeal contractile. #P < 0.05 compared with dry swallow.
Effect on hypopharyngeal IBP.
The average hypopharyngeal IBP progressively increased with increasing external cricoid pressure. This effect was preserved for 5- and 10-ml bolus for all cricoid pressure conditions. For dry swallow, increase in IBP was observed only at high level of restrictive pressure, i.e., 30 mmHg and 40 mmHg (Table 2). Consistent with a previous study (26), the hypopharyngeal IBP increased with bolus volume compared with dry swallow and this volume effect was preserved for any tested cricoid pressure (P < 0.05). Table 2 shows the effect of volume on hypopharyngeal IBP commensurate with each of the tested external cricoid pressures.
Table 2.
Effect of bolus volume and external cricoid pressures on hypopharyngeal intrabolus pressure
| External Cricoid Pressure | DS | 5 ml | 10 ml |
|---|---|---|---|
| 0 mmHg | 3.3 ± 0.8 | 6.8 ± 0.9† | 8.7 ± 0.9† |
| 20 mmHg | 4.8 ± 0.7 | 8.6 ± 1.0*† | 10.6 ± 1.0*† |
| 30 mmHg | 5.1 ± 0.8* | 10.1 ± 1.0*† | 12.2 ± 1.2*† |
| 40 mmHg | 7.0 ± 1.2* | 11.2 ± 1.1*† | 13.0 ± 1.1*† |
Values are mean mmHg ± SE.
P < 0.05 compared with no external cricoid pressure at each tested bolus volume;
P < 0.05 compared with DS at each tested external cricoid pressure.
DISCUSSION
UES opening during swallowing is the end result of the interaction between several factors. These include 1) cessation of the cholinergic tone of the UES, i.e., relaxation; 2) forceful distraction of the cricoid cartilage away from the cricopharyngeus muscle due to contraction of suprahyoid UES opening muscles, i.e., physical opening of the sphincter lumen; 3) distensibility of the UES; and 4) the distending forces of the oncoming swallowed bolus from within the hypopharyngeal and sphincter lumen (2, 8, 9, 12, 24). To date, pathophysiological information about each of these elements and their impact on others and pharyngeal as well as UES deglutitive pressure phenomena has been derived from disease conditions that frequently affect more than one of the above mentioned elements involved in oropharyngeal swallowing, therefore making investigation of the effect of a given element difficult.
In this study, we determined the effect of perturbation of only one of the elements involved in oropharyngeal swallowing namely the UES on pharyngo-UES pressure phenomena. This was achieved by restriction of its opening by applying a range of external cricoid pressures during swallowing of a range of crystalloid volumes. Study findings indicate that short-term restriction of UES opening by external cricoid pressure does not affect the pharyngeal peristaltic pressure amplitude or direction. Therefore, the present model likely resembles an early stage of constricted UES, when the chronic physiological change of diminished UES opening is not yet evident. Whether and to what degree this finding can be extended to long-term UES restriction cannot be addressed in the present study. Earlier studies of a naturally occurring reduction in UES maximum opening during swallowing in the elderly has shown significant increase in the hypopharyngeal peristaltic pressure wave amplitude and duration (25). This finding was not observed for any crystalloid bolus volumes tested in the present study. This discrepancy may be due to the fact that in this study there was not enough time for the effect of increased resistance to UES opening to influence the pharyngeal contractile function.
The findings of the present study show similarities to findings of prior studies of conditions associated with reduced UES opening, such as aging, cricopharyngeal bar, poststroke, and radiation therapy for head and neck malignancies (5, 14, 20, 25). These findings indicated an elevated hypopharyngeal IBP commensurate with the degree of restriction, increased relaxation duration, and increased nadir UES relaxation pressure. In the present study, we did not observe an impaired UES relaxation, which suggests that short-term restriction of the UES by applying external pressure does not interfere with the neurological mechanism of cessation of the cholinergic tone of the cricopharyngeus muscle.
Prior studies have evaluated the effect of bolus volume in a given naturally occurring UES opening reduction in disease conditions and aging. The present study has extended these findings to the outcomes of a gradation of restriction in an experimental setting in individuals with healthy swallowing mechanism. As such the present study provides an opportunity for using the present model for further testing and investigation of abnormal findings in various diseases causing oropharyngeal dysphagia.
In this study, we tested an acute UES restriction model by applying continuous pressure during swallowing on the UES to simulate disease conditions that are accompanied by increased resistance to UES opening. This model is the first to investigate pharyngeal and UES biomechanics for both saliva swallow and water swallows under experimental UES restrictive condition in humans. As described above this model shows close similarities to disease conditions, which cause increased UES resistance including a significant increase in hypopharyngeal IBP, UES nadir deglutitive relaxation pressure, and duration. In addition, it allowed testing of and showed a direct relationship between these changes and the magnitude of restriction. This model also showed that contrary to the oro/hypopharynx, deglutitive velopharyngeal pressure CI progressively increases with increased swallowed volume but is not affected by acute short-term increase in UES resistance.
Earlier studies have shown that hypopharyngeal IBP is a function of resistance to bolus flow offered by the UES and the pharyngeal contraction driving the bolus (4). In the circumstance of normal pharyngeal function, increased hypopharyngeal IBP is most dependent on the UES diameter achieved during deglutitive opening (1). UES accommodates large volumes of swallows by opening wider and longer to maintain IBP within a narrow physiological range (8). Thus IBP is deemed as an indirect measurement of UES compliance (1, 18). In our present model, application of external cricoid pressure impaired UES distention and subsequently altered UES transsphincteric pressure-flow relationship, resulting in increased hypopharyngeal IBP. In addition, the results demonstrated that the increase of hypopharyngeal IBP was proportionate to the extent of UES restriction.
Previous studies have concluded that the dynamics of UES function during deglutition are related to the volume of the swallowed bolus, in that larger boluses are accommodated both by an increased diameter of sphincter opening and by prolongation of the sphincter relaxation (12, 16). The present study confirmed these findings and in addition it showed that with 10-ml bolus swallow, the duration of UES relaxation further increases significantly with applying external cricoid pressure of 30 and 40 mmHg. This finding suggests that, at high level of UES restriction, the UES attempts to remain open longer to overcome higher transsphincteric flow resistance to accommodate larger bolus passage.
In this study, we applied the concept of contractile integral (CI) to quantify the pharyngeal contractility in addition to peak pharyngeal pressure. CI, a summary of contraction amplitude, duration, and spatial domain (mmHg·s·cm), has been widely used to evaluate the overall vigor of contraction in the analysis of esophageal motility (19). It has been suggested to be a more reliable and sensitive index in delineating abnormalities involving sustained or hypertensive esophageal contractions compared with mean or peak pressure (31). Considering the complexity of the pharyngeal swallow sequence, we divided the pharynx into two anatomical segments, the velopharynx and oro/hypopharynx. This was done because of the ease of delineation and to simplify the analysis (32). We set the whole pharyngeal CI as contractile amplitude greater than 20 mmHg from 2 cm above the upper border of UES to consistently isolate the deglutitive data without being confounded by the orad movement of UES during relaxation. We found that external cricoid pressure did not affect the CI of velopharynx or oro/hypopharynx, consistent with the results of analysis of pharyngeal peak pressure and duration of contraction.
Interestingly, although bolus volume had no effect on the amplitude of peristaltic contraction in pharynx, swallowed volume of 5 and 10 ml significantly increased the velopharyngeal CI. It appears that with increasing bolus volumes more powerful velopharyngeal forces are generated. This could represent a mechanism for preventing nasopharyngeal regurgitation with large swallowed volumes and to ensure a tight seal between oral and nasal pharynx to prevent nasal regurgitation when swallowing a large bolus (21). Our findings of the lack of peristaltic pressure increase for larger bolus volumes in the oro/hypopharynx are similar to the prior studies (16, 25).
A previous study has shown that applying cricoid pressure can enhance UES resting pressure to prevent supraesophageal reflux (23). The present study shows that external cricoid pressure can also increase the length of the UES-HPZ. The mechanism of this increase is likely due to the increased approximation of the tissues orad and caudad in relation to the cricopharyngeus muscle toward the posterior wall of the pharyngoesophageal segment by posteriorly directed external pressure.
Limitations of This Study
Although this study offers a novel method for manipulating the UES opening to perturb the swallowing function, it has several limitations. One of the limitations of the present study is the lack of fluoroscopic data about the maximum diameter of deglutitive UES opening commensurate with the external cricoid pressure. This information would have been important for correlating the pressure data with bolus flow rate and UES opening diameters under controlled and predictable perturbation. Videofluoroscopy will be incorporated in future studies now that the model seems to reflect UES disease condition. Another limitation in this study is lack of semisolid bolus swallows such as mashed potatoes and viscous boluses. These boluses were avoided because of safety concerns, since at the time of design and execution of the study the ability of the individuals to handle swallowing was undetermined. Based on the finding of the present study future investigation of these boluses could be safely incorporated. One more limitation in this study is that the study subjects are not healthy volunteers. Although the participants in the present study have supraesophageal reflux symptoms, their UES deglutitive functions were comparable to the published normal values (3). Since in this first study our purpose was to define the effect of various degree of external pressure-induced UES restriction, we did not feel their supraesophageal reflux symptom was a major issue affecting the outcome of the restriction. The complete picture of the model requires data from various age groups and disease conditions.
Conclusion
Acute experimental restriction of UES opening by external cricoid pressure in humans manifests the pressure characteristics of increased resistance to UES transsphincteric flow observed in disorders that are accompanied by reduced UES opening. These pressure characteristics include increased hypopharyngeal IBP as well as nadir deglutitive UES relaxation pressures. This model can potentially be helpful in better understanding of UES pathophysiology of disorders associated with reduced UES opening and increased resistance to transsphincteric flow.
GRANTS
This research was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases Grants R01DK025731 and P01DK068051.
DISCLOSURES
No conflicts of interest, financial or otherwise, are declared by the author(s).
AUTHOR CONTRIBUTIONS
H.J., L.M., T.S., P.S., and R.S. conception and design of research; H.J., L.M., and M.K.K. analyzed data; H.J., L.M., M.K.K., and P.S. drafted manuscript; L.M., M.K.K., and R.S. interpreted results of experiments; L.M. and M.K.K. prepared figures; P.S. and R.S. edited and revised manuscript; R.S. approved final version of manuscript.
REFERENCES
- 1.Ali GN, Wallace KL, Laundl TM, Hunt DR, deCarle DJ, Cook IJ. Predictors of outcome following cricopharyngeal disruption for pharyngeal dysphagia. Dysphagia 12: 133–139, 1997. [DOI] [PubMed] [Google Scholar]
- 2.Asoh R, Goyal RK. Manometry and electromyography of the upper esophageal sphincter in the opossum. Gastroenterology 74: 514–520, 1978. [PubMed] [Google Scholar]
- 3.Bhatia SJ, Shah C. How to perform and interpret upper esophageal sphincter manometry. J Neurogastroenterol Motil 19: 99–103, 2013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Bulow M, Olsson R, Ekberg O. Supraglottic swallow, effortful swallow, and chin tuck did not alter hypopharyngeal intrabolus pressure in patients with pharyngeal dysfunction. Dysphagia 17: 197–201, 2002. [DOI] [PubMed] [Google Scholar]
- 5.Butler SG, Stuart A, Castell D, Russell GB, Koch K, Kemp S. Effects of age, gender, bolus condition, viscosity, and volume on pharyngeal and upper esophageal sphincter pressure and temporal measurements during swallowing. J Speech Lang Hear Res 52: 240–253, 2009. [DOI] [PubMed] [Google Scholar]
- 6.Chaw E, Shem K, Castillo K, Wong SL, Chang J. Dysphagia and associated respiratory considerations in cervical spinal cord injury. Top Spinal Cord Inj Rehabil 18: 291–299, 2012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Clave P, Shaker R. Dysphagia: current reality and scope of the problem. Nat Rev Gastroenterol Hepatol 12: 259–270, 2015. [DOI] [PubMed] [Google Scholar]
- 8.Cook IJ, Dodds WJ, Dantas RO, Massey B, Kern MK, Lang IM, Brasseur JG, Hogan WJ. Opening mechanisms of the human upper esophageal sphincter. Am J Physiol Gastrointest Liver Physiol 257: G748–G759, 1989. [DOI] [PubMed] [Google Scholar]
- 9.Dodds WJ, Stewart ET, Logemann JA. Physiology and radiology of the normal oral and pharyngeal phases of swallowing. AJR Am J Roentgenol 154: 953–963, 1990. [DOI] [PubMed] [Google Scholar]
- 10.Ghosh SK, Pandolfino JE, Zhang Q, Jarosz A, Kahrilas PJ. Deglutitive upper esophageal sphincter relaxation: a study of 75 volunteer subjects using solid-state high-resolution manometry. Am J Physiol Gastrointest Liver Physiol 291: G525–G531, 2006. [DOI] [PubMed] [Google Scholar]
- 11.Humbert IA, Robbins J. Normal swallowing and functional magnetic resonance imaging: a systematic review. Dysphagia 22: 266–275, 2007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Kahrilas PJ, Dodds WJ, Dent J, Logemann JA, Shaker R. Upper esophageal sphincter function during deglutition. Gastroenterology 95: 52–62, 1988. [DOI] [PubMed] [Google Scholar]
- 13.Kalia M. Dysphagia and aspiration pneumonia in patients with Alzheimer's disease. Metabolism 52: 36–38, 2003. [DOI] [PubMed] [Google Scholar]
- 14.Kotz T, Costello R, Li Y, Posner MR. Swallowing dysfunction after chemoradiation for advanced squamous cell carcinoma of the head and neck. Head Neck 26: 365–372, 2004. [DOI] [PubMed] [Google Scholar]
- 15.Lazarus C. Tongue strength and exercise in healthy individuals and in head and neck cancer patients. Semin Speech Lang 27: 260–267, 2006. [DOI] [PubMed] [Google Scholar]
- 16.Leonard R, Rees CJ, Belafsky P, Allen J. Fluoroscopic surrogate for pharyngeal strength: the pharyngeal constriction ratio (PCR). Dysphagia 26: 13–17, 2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Logemann JA. Evaluation and Treatment of Swallowing Disorders. Austin, TX: Pro-Ed, 1998. [Google Scholar]
- 18.Nativ-Zeltzer N, Logemann JA, Zecker SG, Kahrilas PJ. Pressure topography metrics for high-resolution pharyngeal-esophageal manofluorography—a normative study of younger and older adults. Neurogastroenterol Motil 28: 721–731, 2016. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Pandolfino JE, Ghosh SK, Rice J, Clarke JO, Kwiatek MA, Kahrilas PJ. Classifying esophageal motility by pressure topography characteristics: a study of 400 patients and 75 controls. Am J Gastroenterol 103: 27–37, 2008. [DOI] [PubMed] [Google Scholar]
- 20.Perlman AL, Schultz JG, VanDaele DJ. Effects of age, gender, bolus volume, and bolus viscosity on oropharyngeal pressure during swallowing. J Appl Physiol 75: 33–37, 1993. [DOI] [PubMed] [Google Scholar]
- 21.Perry JL. Anatomy and physiology of the velopharyngeal mechanism. Semin Speech Lang 32: 83–92, 2011. [DOI] [PubMed] [Google Scholar]
- 23.Shaker R, Babaei A, Naini SR. Prevention of esophagopharyngeal reflux by augmenting the upper esophageal sphincter pressure barrier. Laryngoscope 124: 2268–2274, 2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Shaker R, Easterling C, Kern M, Nitschke T, Massey B, Daniels S, Grande B, Kazandjian M, Dikeman K. Rehabilitation of swallowing by exercise in tube-fed patients with pharyngeal dysphagia secondary to abnormal UES opening. Gastroenterology 122: 1314–1321, 2002. [DOI] [PubMed] [Google Scholar]
- 25.Shaker R, Ren J, Podvrsan B, Dodds WJ, Hogan WJ, Kern M, Hoffmann R, Hintz J. Effect of aging and bolus variables on pharyngeal and upper esophageal sphincter motor function. Am J Physiol Gastrointest Liver Physiol 264: G427–G432, 1993. [DOI] [PubMed] [Google Scholar]
- 26.Sharma T, Mei L, Jiao H, Shaker R. Nadir UES relaxation and hypopharyngeal intra bolus pressures are more sensitive to consistency and viscosity challenge than pharyngeal peristalsis parameters measured by high resolution manometry. Gastroenterology 146, Suppl 1: S-78, 2014. [Google Scholar]
- 27.Singh S, Hamdy S. Dysphagia in stroke patients. Postgrad Med J 82: 383–391, 2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Starmer HM, Tippett D, Webster K, Quon H, Jones B, Hardy S, Gourin CG. Swallowing outcomes in patients with oropharyngeal cancer undergoing organ-preservation treatment. Head Neck 36: 1392–1397, 2014. [DOI] [PubMed] [Google Scholar]
- 29.Stechmiller JK. Early nutritional screening of older adults: review of nutritional support. J Infus Nurs 26: 170–177, 2003. [DOI] [PubMed] [Google Scholar]
- 30.Sura L, Madhavan A, Carnaby G, Crary MA. Dysphagia in the elderly: management and nutritional considerations. Clin Interv Aging 7: 287–298, 2012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30a.U.S. Congress. Expressing the sense of the Congress that a National Dysphagia Awareness Month should be established, H.Con.Res. 195, 110th Cong., 2nd sess., (Sept. 27, 2008).
- 31.Xiao Y, Kahrilas PJ, Kwasny MJ, Roman S, Lin Z, Nicodeme F, Lu C, Pandolfino JE. High-resolution manometry correlates of ineffective esophageal motility. Am J Gastroenterol 107: 1647–1654, 2012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Yoon KJ, Park JH, Park JH, Jung IS. Videofluoroscopic and manometric evaluation of pharyngeal and upper esophageal sphincter function during swallowing. J Neurogastroenterol Motil 20: 352–361, 2014. [DOI] [PMC free article] [PubMed] [Google Scholar]