0
Original Research: SLEEP MEDICINE |

Upper Esophageal Sphincter and Gastroesophageal Junction Pressure Changes Act to Prevent Gastroesophageal and Esophagopharyngeal Reflux During Apneic Episodes in Patients With Obstructive Sleep Apnea FREE TO VIEW

Shiko Kuribayashi, MD; Benson T. Massey, MD; Muhammad Hafeezullah, MBBS; Lilani Perera, MD; Syed Q. Hussaini, MD; Linda Tatro; Ronald J. Darling, MD; Rose Franco, MD, FCCP; Reza Shaker, MD
Author and Funding Information

From the Dysphagia Institute, Division of Gastroenterology and Hepatology (Drs Kuribayashi, Massey, Hafeezullah, Perera, Hussaini, and Shaker, and Ms Tatro), the Department of Otolaryngology (Dr Darling), and the Department of Sleep Medicine (Dr Franco), Medical College of Wisconsin, Milwaukee, WI.

Correspondence to: Reza Shaker, MD, Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226; e-mail: rshaker@mcw.edu


For editorial comment see page 747

Funding/Support: This study was supported in part by Esophageal Motor Function in Health and Disease [Grant 5R01DK025731-28] and Program Project [Grant 5P01DK068051-03].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;137(4):769-776. doi:10.1378/chest.09-0913
Text Size: A A A
Published online

Background:  Gastroesophageal reflux (GER) is thought to be induced by decreasing intraesophageal pressure during obstructive sleep apnea (OSA). However, pressure changes in the upper esophageal sphincter (UES) and gastroesophageal junction (GEJ) pressure during OSA events have not been measured. The aim of this study was to determine UES and GEJ pressure change during OSA and characterize the GER and esophagopharyngeal reflux (EPR) events during sleep.

Methods:  We studied 15 controls, nine patients with GER disease (GERD) and without OSA, six patients with OSA and without GERD, and 11 patients with both OSA and GERD for 6 to 8 h postprandially during sleep. We concurrently recorded the following: (1) UES, GEJ, esophageal body (ESO), and gastric pressures by high-resolution manometry; (2) pharyngeal and esophageal reflux events by impedance and pH recordings; and (3) sleep stages and respiratory events using polysomnography. End-inspiration UES, GEJ, ESO, and gastric pressures over intervals of OSA were averaged in patients with OSA and compared with average values for randomly selected 10-s intervals during sleep in controls and patients with GERD.

Results:  ESO pressures decreased during OSA events. However, end-inspiratory UES and GEJ pressures progressively increased during OSA, and at the end of OSA events were significantly higher than at the beginning (P < .01). The prevalence of GER and EPR events during sleep in patients with OSA and GERD did not differ from those in controls, patients with GERD and without OSA, and patients with OSA and without GERD.

Conclusions:  Despite a decrease in ESO pressure during OSA events, compensatory changes in UES and GEJ pressures prevent reflux.

Figures in this Article

It has been thought that patients with obstructive sleep apnea (OSA) have more reflux events than healthy subjects.1 In patients with OSA, end-inspiratory intraesophageal pressure progressively decreases during periods of apnea.2 Moreover, nasal continuous positive airway pressure (CPAP) reduces nocturnal gastroesophageal reflux (GER) events in patients with OSA.3,4 Taken together, these findings suggest that the decrease in intraesophageal pressure during OSA could potentially facilitate GER events. However, pressure changes in the upper esophageal sphincter (UES) and gastroesophageal junction (GEJ) during apneic periods have not been measured. Therefore, the pathophysiologic contribution of the decrease in intraesophageal pressure to the development of reflux remains unclear. The aim of the present study was to determine UES and GEJ pressure changes during OSA events and to characterize the GER and esophagopharyngeal reflux (EPR) events during apneic events.

Subject Selection

A total of 41 subjects were enrolled in this study. Subject groups were as follows: 15 healthy subjects (seven men, aged 18-56 years); nine patients with gastroesophageal reflux disease (GERD) and without OSA (five men, aged 18-39 years); six patients with OSA and without GERD (four men, aged 28-54 years), and 11 patients with both OSA and GERD (eight men, aged 26-66 years). None of the subjects had previous gastrointestinal surgery. The healthy subjects had no reflux symptoms or reflux changes at unsedated transnasal endoscopy (TEGD). They also lacked symptoms of sleep disturbance and had a normal screening polysomnography. All GERD patients had erosive esophagitis (on screening study TEGD or during an endoscopy performed for clinical evaluation within 2 years of the study) or had a negative endoscopy but typical reflux symptoms responsive to acid suppressive therapy. All patients with sleep apnea had evidence of OSA, either on a polysomnographic study performed for clinical evaluation within the preceding 2 years or during a screening examination as part of this study. The study protocol was approved by the Medical College of Wisconsin Institutional Review Board, and informed consent was obtained from each subject.

TEGD

TEGD5 was performed without sedation using a 5.4-mm-diameter endoscope (Pentax; Tokyo, Japan) in the sitting position after at least a 6-h fast. TEGD was conducted to evaluate the presence of erosive esophagitis and to confirm the absence of Barrett esophagus and large hiatal hernia. This was performed on all subjects not having an endoscopy for clinical indications within the preceding 2 years.

Polysomnography

Alice 5 (Respironics; Murrysville, PA) or Sandman Elite (Nellcor Puritan Bennett Inc.; Kanata, ON, Canada) were used to conduct the polysomnography (PSG). PSG was performed in all subjects and included EEG, ECG, electroophthalomogram, electromyogram (chin and legs), respiratory measurements (chest and abdomen), nasal airflow, pulse oximetry, and snoring measurement. PSG was used to detect sleep stages, arousals, and respiratory events during sleep. Polysomnography was performed as a screening test on all subjects without such a study for clinical evaluation within the previous 2 years.

Manometry

A solid-state manometric assembly with 36 circumferential sensors spaced in 1-cm intervals (outer diameter, 4.2 mm) was used (Sierra Scientific Instruments Inc.; Los Angeles, CA). Before the recording, the transducers were calibrated and a thermal compensation program was applied using external pressure.

Impedance/pH Recordings

A 1.5-mm-diameter Comfortec multiluminal impedance/pH probe (Sandhill Scientific; Highlands Ranch, CO) was used. This probe has six-channel impedance sites and two-channel pH sensors. The pH sensors were calibrated before the study using standard pH 4 and 7 buffers. Impedance/pH recordings were used to detect the features of refluxate, such as liquid or gas, or acid or nonacid.

Synchronizing Devices

Two synchronization methods were used. The first method involved the input of a timing signal produced by a synchronization signal generator (Sandhill Scientific) to both impedance/pH recordings and the PSG. The second method involved video recording an image that showed the manometric device time in the PSG monitor.

Study Protocol

Study subjects reported to the sleep laboratory in the evening after a 6-h fast. Patients with GERD who were taking medications for their reflux symptoms stopped taking those 2 days before both the awake and sleep studies. Subjects who were taking sleep aids stopped taking those 2 days before the sleep study. In addition, patients with OSA who were using CPAP did not use it during the sleep study. The nasal passage was anesthetized with 2% lidocaine jelly. The manometric assembly was passed transnasally and positioned to record from the hypopharynx to the stomach. After confirming the position of the UES and GEJ, an impedance/pH catheter was placed via the same or the other nare. The proximal pH sensor was placed 2 cm above the proximal end of the UES high pressure zone, and the distal pH sensor was positioned 5 cm above the proximal end of the GEJ high pressure zone. The two proximal impedance sites were positioned in the hypopharynx, and the two distal impedance sites were positioned in the distal esophagus. The remaining two middle impedance sites were positioned in the proximal or middle esophagus.

After the catheters were positioned, the subjects ate a 1,000 calorie meal (cheeseburger) with 350 mL of carbonated soda. After completion of the meal, the subjects additionally had the PSG sensors placed. Recordings in the sleep study started in a supine position approximately 1 h after the meal and continued for 6 to 8 h.

Data Analysis

Manometric data and impedance/pH recordings were analyzed with ManoView (Sierra Scientific Instruments, Inc.) and Bioview (Sandhill Scientific), manually. An E-sleeve was applied on both the UES and GEJ to measure these pressures.6 The E-sleeve technique displays on a single channel the highest instantaneous pressure reading from any of the several pressure sensors located within the defined E-sleeve zone; this allows the tracking of pressure increases in sphincter segments that may move axially off of any single point-sensor during respiratory movements. One esophageal manometric site free of vascular effect was selected to measure intraesophageal pressure. One manometric site in the stomach was selected to measure intragastric pressure. Sleep stages and respiratory events recorded during PSG were scored by a registered polysomnographic technologist. The sleep stages, arousal events, and respiratory events were all scored using standardized criteria.7 The apnea-hypopnea index (AHI) was calculated as the number of apneic or hypoapneic events per hour during sleep (the total number of apneic or hypoapneic events/total sleep time). Patients with OSA were defined as patients whose AHI was > 5.

GER was assessed using the impedance/pH recordings. Liquid reflux was identified by an orally progressing decrease in impedance, beginning at the most distal impedance sensor and propagating to more proximal impedance measuring segments.8 Gas reflux was detected when intraluminal air, which has a very low electrical conductivity, produced a rapid and pronounced rise in impedance.9 Mixed reflux was detected as an event in which features of both liquid reflux and gas reflux were seen. For the analyses in this study, pure liquid, pure gas, and mixed liquid-gas GER events were pooled and analyzed as reflux events regardless of whether the pH fell below 4. EPR episodes were identified when retrograde impedance changes at the hypopharynx were detected during GER episodes. EPR events were also classified in the same manner as GER events for the analysis.

Apneic events were identified and marked on the polysomnographic recording. Using the above synchronization methods, the times of these events were analyzed for pressure changes and reflux events on the manometric and impedance/pH recordings, respectively. UES, intraesophageal, GEJ, and gastric pressures at both end-inspiratory and end-expiratory phases were measured at both the onset and end of OSA in patients with OSA. For subjects without apneic events, similar pressure readings were obtained from the beginning and end of five randomly selected 10-s intervals during sleep.

Identified apneic episodes were examined carefully for evidence of concurrent transient lower esophageal sphincter relaxations (TLESRs) and reflux events on impedance/pH monitoring. OSA events that were accompanied with TLESR events were excluded for the UES, intraesophageal, GEJ, and gastric pressure measurements during OSA.

Statistical Analysis

A signed rank test was used to compare the UES, intraesophageal, GEJ, and gastric pressures between the onset and end of OSA in patients with OSA or between the onset and end of randomly selected 10-s intervals in healthy subjects and patients with GERD and without apnea. The Kruskal-Wallis test was used to compare total sleep time and the number of GER, GER during sleep, EPR, and EPR during sleep events between healthy subjects, patients with GERD, patients with OSA, and patients with GERD and OSA. The Kruskal-Wallis test was used to compare the magnitude of pressure changes in the UES, esophageal body (ESO), GEJ, and gastric sites among the different subject groups. Dunn’s method was used for the pairwise multiple comparison. Data in the text are given as median and 25% to 75% CIs unless stated otherwise.

There was no difference in total sleep time among the four groups (Table 1). There was also no difference in the numbers of total GER events, GER events during sleep, total EPR events, and EPR events during sleep (Table 1). No EPR events during sleep were found in patients with OSA, either with or without GERD. A total of 542 OSA events were observed in patients with OSA and without GERD, and 448 OSA events in patients with OSA and GERD. The duration of OSA events was 16 s (25% to 75%, range 12-22) in patients with OSA and without GERD and 16 s (12-21) in patients with OSA and GERD.

Table Graphic Jump Location
Table 1 —Demographic Data in Each Group

Data are median (25% CI, 75% CI). AHI = apnea-hypopnea index; EPR = esophagopharyngeal reflux; GEJ = gastroesophageal junction; GER = gastroesophageal reflux; GERD = gastroesophageal reflux disease; OSA = obstructive sleep apnea; TLESR = transient lower esophageal sphincter relaxation.

A total of nine apneic events were identified in four patients with OSA (three with GERD), in which the interval of the apneic event overlapped partially or completely the interval of a TLESR event. None of these had evidence for GER or EPR on either impedance or pH recordings. During these nine episodes, the inhibition of inspiratory phasic increases in GEJ pressure seen during the TLESR persisted; that is, the typical response of increasing end-inspiratory GEJ pressures with apnea did not supplant the TLESR response. However, the progressive increase in UES pressures during apnea was not affected by the TLESR.

Two examples of apneic events with associated pressure changes are seen in Figures 1 and 2. Over the course of the apneic events, progressive changes were seen in the intraesophageal, UES, and GEJ pressures. Thus, the intraesophageal pressure at the end-inspiratory phase at the end of OSA was significantly lower than that at the beginning of OSA (P < .01, Table 2). In contrast, both the UES and GEJ pressures at the end-inspiratory phase at the end of OSA were significantly higher than those at the beginning of OSA (P < .01, Table 2). Gastric pressure at the end-inspiratory phase was not different at the onset and end of OSA. Pressures at the end-expiratory phase at the end of OSA in the UES, esophagus, GEJ, and stomach were similar to those at the beginning of OSA. The magnitude of the GEJ pressure increase during the apneic events was similar in patients with OSA with and without GERD. These two patient groups were significantly different in the magnitude of the pressure changes during apneic events in the ESO and UES; however, the trend for these differences would actually make reflux less likely in the patients with OSA and with GERD than those without GERD (Table 2).

Figure Jump LinkFigure 1. Concurrent polysomnographic and manometric tracings from a typical OSA event are shown. (A) This tracing represents a 60-s period from the polysomnogram recording. The normally fluctuating nasal airflow and pressure become flat, indicating an apneic event. There is persistent effort seen in the chest and abdomen belts, confirming the obstructive nature of the apnea. There is no rapid eye movement, and both submental and leg muscle tone continue to persist. These findings indicate a non-rapid eye movement sleep stage. There is an absence of Δ waves and the presence of sleep spindles, indicating stage 2 sleep. Therefore, in this example, the OSA event occurred during stage 2 sleep and lasted 26 s. This obstructive event ended with arousal, seen in the EEG channels and confirmed with the return of normal nasal airflow. (B) Concurrent high-resolution manometric contour plot tracing during the apneic period seen in (A). This tracing represents a 60-s period. The horizontal axis represents time, and the vertical axis represents axial location along the pharynx, UES, esophagus, GEJ, and stomach. Pressure values are coded through a color scale. Color bands denoting the UES and GEJ high pressure zones are readily identified, as are phasic changes in pressure with respiration. The time of the OSA event is shown as a blue box at the bottom of the tracing. (C) Line tracing and e-sleeve pressure tracings of pressure data seen in (B). Figure shows selected pressure recordings from individual recording sites used to generate the contour plot. In addition, the e-sleeve shows the highest instantaneous pressure value over multiple sensors located at the level of the GEJ, to avoid artifacts from recording from a single sensor that is displaced during respiration. The end-inspiratory intraesophageal pressure progressively decreases from the beginning to the end of the apneic period. On the other hand, the end-inspiratory GEJ pressure progressively increases from the beginning to the end of the apneic period. (D) UES pressure response during the apneic period. Tracing is similar to that in (C), except that the e-sleeve is now positioned over the region of the UES. The end-inspiratory UES pressure increases progressively from the beginning to the end of the apneic period. EMG = electromyogram; EOG = electroophthalomogram; ESO = esophageal body; GEJ = gastroesophageal junction; LES = lower esophageal sphincter; L-EOG = left electroophthalmogram; L-LEG = electromyogram on the left leg; R-EOG = right electroophthalmogram, R-LEG = electromyogram on the right leg; OSA = obstructive sleep apnea; Sao2 = arterial oxygen saturation; UES = upper esophageal sphincter.Grahic Jump Location
Figure Jump LinkFigure 2. Another example of an apneic event during stage 2 sleep. Apnea begins immediately following a deep inspiration and is accompanied by pressure increases in the regions of the UES and GEJ during the course of the apnea event. See Figure 1 legend for description of tracing definitions and for expansion of abbreviations.Grahic Jump Location
Table Graphic Jump Location
Table 2 —End-Inspiratory and End-Expiratory Pressure Changes at the Onset and End of OSA Events in Patients With OSA or at the Onset and End of Randomly Selected 10-s Intervals in Subjects Without OSA

Data are median (25% CI, 75% CI). Units are mm Hg. ESO = esophageal body; UES = upper esophageal sphincter. See Table 1 for expansion of other abbreviations.

a 

P < .01 between the onset and end of OSA events.

b 

P < .05 against healthy subjects and patients with GERD.

c 

P < .05 against patients with OSA.

There were no differences of pressures in the UES, intraesophageal area, GEJ, and stomach between the start and end of randomly selected 10-s intervals in both healthy subjects and patients with GERD and without OSA (Table 2). The major findings regarding pressure changes in all four groups are depicted in Figure 3.

Figure Jump LinkFigure 3. Box plots show changes in end-inspiratory pressures between onset and end of apneic events (C, D) or random 10-s intervals (A, B). Boxes represent the 25% to 75% range, and horizontal bar is the median. A = healthy subjects; B = patients with GERD and without OSA; C = OSA patients with OSA and without GERD; D = GERD patients with GERD and OSA; GERD = gastroesophageal reflux disease. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location

During apneic events, we also observed a progressive fall in end-inspiratory hypopharyngeal pressure as the apneic event progressed. This was not unexpected, as the level of obstruction is above this region in patients with OSA, and changes in intrathoracic pressure will also be manifest in the hypopharynx via the open glottis.

In the present study, we confirmed that the intraesophageal pressure does decrease during OSA events. However, we also found that this decrease is counterbalanced by an increase in UES and GEJ pressures during apnea, with changes of a magnitude to preclude both GER and EPR. The pressure changes with inspiration at the GEJ likely result from contraction of the diaphragmatic crura, rather than from a change in the tone of the smooth muscle lower esophageal sphincter (LES), based on prior work showing that phasic changes in pressure in this region during respiration are closely associated with electrical activity of this muscle.10,11 As a consequence, no GER or EPR events were seen during apnea. The prevalence of GER and EPR events in patients with OSA was similar to that in both healthy subjects and patients with GERD. According to these findings, OSA does not seem to induce either GER or EPR events.

Previous studies have found a high prevalence of GER symptoms as well as endoscopic reflux changes and abnormal results of 24-h ambulatory esophageal pH monitoring in patients with OSA.12-14 However, there is often poor correlation between the severity of GERD and OSA findings.12,14 Thus, it is unclear if there is a mechanistic link between the pathophysiologic abnormalities of OSA and the generation of GER events. Several possible mechanisms have been proposed. One is that OSA induces more nocturnal arousals, and it is known that TLESRs, which are the major mechanisms for GER, occur following such arousals much more than during deep sleep.15,16 Indeed, the only study to date to examine the temporal correlation between concurrently recorded apneic events and pH drops showed that reflex events were associated with arousal events, not apneic events.16

Another potential mechanism is the reduction in intraesophageal body pressure during apneic events, which could create a pressure differential between the esophageal and gastric lumens that would favor retrograde passage of gastric contents into the esophagus. However, for this mechanism of reflux to occur, there needs to be a reduction of GEJ pressure to less than gastric pressure. No previous study has actually measured concurrent pressures within the regions of the stomach, GEJ, ESO, and UES during apneic episodes in patients with OSA. A major strength of our study was the ability to assess all of these pressure changes along with concurrent measurements of possible acid and nonacid reflux during precisely identified apneic events. However, the findings of our study disprove this possible mechanism, likely explaining the prior findings of reflux during arousal rather than during apnea.

Inspiratory accentuation of UES pressure is a well-known phenomenon17 that can also be observed during sleep.18 The mechanisms and neural pathways responsible for the association between these two motor events currently remain obscure, as do the factors driving the greater inspiratory response of the UES over the course of an apneic event.

Previous work has indicated that CPAP treatment can reduce the magnitude of reflux in patients with concurrent GERD and sleep apnea.3,4 Proposed mechanisms for the benefit of CPAP include decreased arousals, elevation of intraesophageal pressure, and even elevations in GEJ pressure.19 Based on the findings from our study, the latter two changes are not likely to be of actual benefit, since the pressure changes in response to apnea are already in a direction to prevent reflux.

It is of interest that while patients with OSA and GERD in our study showed a similar pattern of pressure change to patients with OSA and without GERD, the magnitude of the changes (greater UES pressure increase and smaller ESO pressure decrease) would make the patients with GERD actually less at risk for reflux events. The reason for the differences in these two patient groups is unclear; they did not differ significantly in terms of age, gender, BMI, or number of apneic events.

There are some limitations to our study. We did not study patients with large, fixed hiatal hernias, wherein anatomic separation of the smooth muscle LES from the level of the crural diaphragm can predispose patients to reflux via mechanisms other than TLESR, such as re-reflux and swallow-associated reflux.20 We also did not study patients with severe motor disturbance, such as with hypotonic LES or UES or impaired ESO peristalsis. Again, such patients could have reflux by mechanisms such as stress reflux across a hypotonic sphincter as well as impaired clearance of refluxate. The number of subjects studied was also small, although the major findings in our study were consistent throughout the patient groups. Our apneic events were somewhat shorter than is often seen, and this may have resulted in smaller falls in intrathoracic pressure during the apneic episodes. It is unclear if this was the result of the additional instrumentation for this study, an effect of studying subjects in the immediate postprandial period, or a difference in our study population. Our patients with apnea also had previous experience with CPAP, and this may have some effect on sensation in the upper airway. Finally, while we did not observe reflux events during the rare TLESRs that overlapped periods of apnea in this study, it is quite possible that the cooccurrence of these two phenomena could predispose other patients in other clinical settings to reflux during apnea.

Despite a decrease in intraesophageal pressure during OSA events, compensatory changes in UES and GEJ pressures act to prevent patients with OSA with or without GERD from having either acid or nonacid reflux events during periods of apnea.

Author contributions:Dr Kuribuyashi: contributed to study concept and design, enrolling patients and volunteers, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and statistical analysis.

Dr Massey: contributed to study concept and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important content, and statistical analysis.

Dr Hafeezullah: contributed to enrolling patients and volunteers; acquisition of data; and administrative, technical, and material support.

Dr Perera: contributed to acquisition of data, and analysis and interpretation of data.

Dr Hussaini: contributed to enrolling patients and volunteers, and administrative, technical, and material support.

Ms Tatro: contributed to enrolling patients and volunteers, and administrative, technical, and material support.

Dr Darling: contributed to enrolling patients and volunteers.

Dr Franco: contributed to critical revision of the manuscript for important intellectual content.

Dr Shaker: contributed to study concept and design, analysis and interpretation of data, critical revision of the manuscript for important intellectual content, and obtaining funding.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

AHI

apnea-hypopnea index

CPAP

continuous positive airway pressure

EPR

esophagopharyngeal reflux

ESO

esophageal body

GEJ

gastroesophageal junction

GER

gastroesophageal reflux

GERD

gastroesophageal reflux disease

LES

lower esophageal sphincter

OSA

obstructive sleep apnea

PSG

polysomnography

TEGD

transnasal endoscopy

TLESR

transient lower esophageal sphincter relaxation

UES

upper esophageal sphincter

Berg S, Hoffstein V, Gislason T. Acidification of distal esophagus and sleep-related breathing disturbances. Chest. 2004;1256:2101-2106. [CrossRef] [PubMed]
 
Zamagni M, Sforza E, Boudewijns A, Petiau C, Krieger J. Respiratory effort. A factor contributing to sleep propensity in patients with obstructive sleep apnea. Chest. 1996;1093:651-658. [CrossRef] [PubMed]
 
Kerr P, Shoenut JP, Millar T, Buckle P, Kryger MH. Nasal CPAP reduces gastroesophageal reflux in obstructive sleep apnea syndrome. Chest. 1992;1016:1539-1544. [CrossRef] [PubMed]
 
Tawk M, Goodrich S, Kinasewitz G, Orr W. The effect of 1 week of continuous positive airway pressure treatment in obstructive sleep apnea patients with concomitant gastroesophageal reflux. Chest. 2006;1304:1003-1008. [CrossRef] [PubMed]
 
Shaker R. Unsedated trans-nasal pharyngoesophagogastroduodenoscopy (T-EGD): technique. Gastrointest Endosc. 1994;403:346-348. [CrossRef] [PubMed]
 
Clouse RE, Parks TR, Staiano A, et al. Creation of an electronic sleeve emulation (eSleeve) for use with solid-state high-resolution manometry (HRM). Gastroenterology. 2004;126Suppl 2:A-111
 
Iber C, Ancoli-Israel S, Chesson AL Jr, et al. The AASM Manual for the Scoring of Sleep and Associated Events. 2007; Westchester, IL American Academy of Sleep Medicine
 
Skopnik H, Silny J, Heiber O, Schulz J, Rau G, Heimann G. Gastroesophageal reflux in infants: evaluation of a new intraluminal impedance technique. J Pediatr Gastroenterol Nutr. 1996;235:591-598. [CrossRef] [PubMed]
 
Sifrim D, Silny J, Holloway RH, Janssens JJ. Patterns of gas and liquid reflux during transient lower oesophageal sphincter relaxation: a study using intraluminal electrical impedance. Gut. 1999;441:47-54. [CrossRef] [PubMed]
 
Mittal RK, Rochester DF, McCallum RW. Electrical and mechanical activity in the human lower esophageal sphincter during diaphragmatic contraction. J Clin Invest. 1988;814:1182-1189. [CrossRef] [PubMed]
 
Martin CJ, Dodds WJ, Liem HH, Dantas RO, Layman RD, Dent J. Diaphragmatic contribution to gastroesophageal competence and reflux in dogs. Am J Physiol. 1992;2634 Pt 1:G551-G557. [PubMed]
 
Graf KI, Karaus M, Heinemann S, Körber S, Dorow P, Hampel KE. Gastroesophageal reflux in patients with sleep apnea syndrome. Z Gastroenterol. 1995;3312:689-693. [PubMed]
 
Demeter P, Visy KV, Magyar P. Correlation between severity of endoscopic findings and apnea-hypopnea index in patients with gastroesophageal reflux disease and obstructive sleep apnea. World J Gastroenterol. 2005;116:839-841. [PubMed]
 
Morse CA, Quan SF, Mays MZ, Green C, Stephen G, Fass R. Is there a relationship between obstructive sleep apnea and gastroesophageal reflux disease? Clin Gastroenterol Hepatol. 2004;29:761-768. [CrossRef] [PubMed]
 
Freidin N, Fisher MJ, Taylor W, et al. Sleep and nocturnal acid reflux in normal subjects and patients with reflux oesophagitis. Gut. 1991;3211:1275-1279. [CrossRef] [PubMed]
 
Penzel T, Becker HF, Brandenburg U, Labunski T, Pankow W, Peter JH. Arousal in patients with gastro-oesophageal reflux and sleep apnoea. Eur Respir J. 1999;146:1266-1270. [CrossRef] [PubMed]
 
Goyal RK, Sangree MH, Hersh T, Spiro HM. Pressure inversion point at the upper high pressure zone and its genesis. Gastroenterology. 1970;595:754-759. [PubMed]
 
Kahrilas PJ, Dodds WJ, Dent J, Haeberle B, Hogan WJ, Arndorfer RC. Effect of sleep, spontaneous gastroesophageal reflux, and a meal on upper esophageal sphincter pressure in normal human volunteers. Gastroenterology. 1987;922:466-471. [PubMed]
 
Shepherd KL, Holloway RH, Hillman DR, Eastwood PR. The impact of continuous positive airway pressure on the lower esophageal sphincter. Am J Physiol Gastrointest Liver Physiol. 2007;2925:G1200-G1205. [CrossRef] [PubMed]
 
Mittal RK, Lange RC, McCallum RW. Identification and mechanism of delayed esophageal acid clearance in subjects with hiatus hernia. Gastroenterology. 1987;921:130-135. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Concurrent polysomnographic and manometric tracings from a typical OSA event are shown. (A) This tracing represents a 60-s period from the polysomnogram recording. The normally fluctuating nasal airflow and pressure become flat, indicating an apneic event. There is persistent effort seen in the chest and abdomen belts, confirming the obstructive nature of the apnea. There is no rapid eye movement, and both submental and leg muscle tone continue to persist. These findings indicate a non-rapid eye movement sleep stage. There is an absence of Δ waves and the presence of sleep spindles, indicating stage 2 sleep. Therefore, in this example, the OSA event occurred during stage 2 sleep and lasted 26 s. This obstructive event ended with arousal, seen in the EEG channels and confirmed with the return of normal nasal airflow. (B) Concurrent high-resolution manometric contour plot tracing during the apneic period seen in (A). This tracing represents a 60-s period. The horizontal axis represents time, and the vertical axis represents axial location along the pharynx, UES, esophagus, GEJ, and stomach. Pressure values are coded through a color scale. Color bands denoting the UES and GEJ high pressure zones are readily identified, as are phasic changes in pressure with respiration. The time of the OSA event is shown as a blue box at the bottom of the tracing. (C) Line tracing and e-sleeve pressure tracings of pressure data seen in (B). Figure shows selected pressure recordings from individual recording sites used to generate the contour plot. In addition, the e-sleeve shows the highest instantaneous pressure value over multiple sensors located at the level of the GEJ, to avoid artifacts from recording from a single sensor that is displaced during respiration. The end-inspiratory intraesophageal pressure progressively decreases from the beginning to the end of the apneic period. On the other hand, the end-inspiratory GEJ pressure progressively increases from the beginning to the end of the apneic period. (D) UES pressure response during the apneic period. Tracing is similar to that in (C), except that the e-sleeve is now positioned over the region of the UES. The end-inspiratory UES pressure increases progressively from the beginning to the end of the apneic period. EMG = electromyogram; EOG = electroophthalomogram; ESO = esophageal body; GEJ = gastroesophageal junction; LES = lower esophageal sphincter; L-EOG = left electroophthalmogram; L-LEG = electromyogram on the left leg; R-EOG = right electroophthalmogram, R-LEG = electromyogram on the right leg; OSA = obstructive sleep apnea; Sao2 = arterial oxygen saturation; UES = upper esophageal sphincter.Grahic Jump Location
Figure Jump LinkFigure 2. Another example of an apneic event during stage 2 sleep. Apnea begins immediately following a deep inspiration and is accompanied by pressure increases in the regions of the UES and GEJ during the course of the apnea event. See Figure 1 legend for description of tracing definitions and for expansion of abbreviations.Grahic Jump Location
Figure Jump LinkFigure 3. Box plots show changes in end-inspiratory pressures between onset and end of apneic events (C, D) or random 10-s intervals (A, B). Boxes represent the 25% to 75% range, and horizontal bar is the median. A = healthy subjects; B = patients with GERD and without OSA; C = OSA patients with OSA and without GERD; D = GERD patients with GERD and OSA; GERD = gastroesophageal reflux disease. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Demographic Data in Each Group

Data are median (25% CI, 75% CI). AHI = apnea-hypopnea index; EPR = esophagopharyngeal reflux; GEJ = gastroesophageal junction; GER = gastroesophageal reflux; GERD = gastroesophageal reflux disease; OSA = obstructive sleep apnea; TLESR = transient lower esophageal sphincter relaxation.

Table Graphic Jump Location
Table 2 —End-Inspiratory and End-Expiratory Pressure Changes at the Onset and End of OSA Events in Patients With OSA or at the Onset and End of Randomly Selected 10-s Intervals in Subjects Without OSA

Data are median (25% CI, 75% CI). Units are mm Hg. ESO = esophageal body; UES = upper esophageal sphincter. See Table 1 for expansion of other abbreviations.

a 

P < .01 between the onset and end of OSA events.

b 

P < .05 against healthy subjects and patients with GERD.

c 

P < .05 against patients with OSA.

References

Berg S, Hoffstein V, Gislason T. Acidification of distal esophagus and sleep-related breathing disturbances. Chest. 2004;1256:2101-2106. [CrossRef] [PubMed]
 
Zamagni M, Sforza E, Boudewijns A, Petiau C, Krieger J. Respiratory effort. A factor contributing to sleep propensity in patients with obstructive sleep apnea. Chest. 1996;1093:651-658. [CrossRef] [PubMed]
 
Kerr P, Shoenut JP, Millar T, Buckle P, Kryger MH. Nasal CPAP reduces gastroesophageal reflux in obstructive sleep apnea syndrome. Chest. 1992;1016:1539-1544. [CrossRef] [PubMed]
 
Tawk M, Goodrich S, Kinasewitz G, Orr W. The effect of 1 week of continuous positive airway pressure treatment in obstructive sleep apnea patients with concomitant gastroesophageal reflux. Chest. 2006;1304:1003-1008. [CrossRef] [PubMed]
 
Shaker R. Unsedated trans-nasal pharyngoesophagogastroduodenoscopy (T-EGD): technique. Gastrointest Endosc. 1994;403:346-348. [CrossRef] [PubMed]
 
Clouse RE, Parks TR, Staiano A, et al. Creation of an electronic sleeve emulation (eSleeve) for use with solid-state high-resolution manometry (HRM). Gastroenterology. 2004;126Suppl 2:A-111
 
Iber C, Ancoli-Israel S, Chesson AL Jr, et al. The AASM Manual for the Scoring of Sleep and Associated Events. 2007; Westchester, IL American Academy of Sleep Medicine
 
Skopnik H, Silny J, Heiber O, Schulz J, Rau G, Heimann G. Gastroesophageal reflux in infants: evaluation of a new intraluminal impedance technique. J Pediatr Gastroenterol Nutr. 1996;235:591-598. [CrossRef] [PubMed]
 
Sifrim D, Silny J, Holloway RH, Janssens JJ. Patterns of gas and liquid reflux during transient lower oesophageal sphincter relaxation: a study using intraluminal electrical impedance. Gut. 1999;441:47-54. [CrossRef] [PubMed]
 
Mittal RK, Rochester DF, McCallum RW. Electrical and mechanical activity in the human lower esophageal sphincter during diaphragmatic contraction. J Clin Invest. 1988;814:1182-1189. [CrossRef] [PubMed]
 
Martin CJ, Dodds WJ, Liem HH, Dantas RO, Layman RD, Dent J. Diaphragmatic contribution to gastroesophageal competence and reflux in dogs. Am J Physiol. 1992;2634 Pt 1:G551-G557. [PubMed]
 
Graf KI, Karaus M, Heinemann S, Körber S, Dorow P, Hampel KE. Gastroesophageal reflux in patients with sleep apnea syndrome. Z Gastroenterol. 1995;3312:689-693. [PubMed]
 
Demeter P, Visy KV, Magyar P. Correlation between severity of endoscopic findings and apnea-hypopnea index in patients with gastroesophageal reflux disease and obstructive sleep apnea. World J Gastroenterol. 2005;116:839-841. [PubMed]
 
Morse CA, Quan SF, Mays MZ, Green C, Stephen G, Fass R. Is there a relationship between obstructive sleep apnea and gastroesophageal reflux disease? Clin Gastroenterol Hepatol. 2004;29:761-768. [CrossRef] [PubMed]
 
Freidin N, Fisher MJ, Taylor W, et al. Sleep and nocturnal acid reflux in normal subjects and patients with reflux oesophagitis. Gut. 1991;3211:1275-1279. [CrossRef] [PubMed]
 
Penzel T, Becker HF, Brandenburg U, Labunski T, Pankow W, Peter JH. Arousal in patients with gastro-oesophageal reflux and sleep apnoea. Eur Respir J. 1999;146:1266-1270. [CrossRef] [PubMed]
 
Goyal RK, Sangree MH, Hersh T, Spiro HM. Pressure inversion point at the upper high pressure zone and its genesis. Gastroenterology. 1970;595:754-759. [PubMed]
 
Kahrilas PJ, Dodds WJ, Dent J, Haeberle B, Hogan WJ, Arndorfer RC. Effect of sleep, spontaneous gastroesophageal reflux, and a meal on upper esophageal sphincter pressure in normal human volunteers. Gastroenterology. 1987;922:466-471. [PubMed]
 
Shepherd KL, Holloway RH, Hillman DR, Eastwood PR. The impact of continuous positive airway pressure on the lower esophageal sphincter. Am J Physiol Gastrointest Liver Physiol. 2007;2925:G1200-G1205. [CrossRef] [PubMed]
 
Mittal RK, Lange RC, McCallum RW. Identification and mechanism of delayed esophageal acid clearance in subjects with hiatus hernia. Gastroenterology. 1987;921:130-135. [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
Guidelines
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543