Esophageal Functional Changes in Obstructive Sleep Apnea/Hypopnea Syndrome and Their Impact on Laryngopharyngeal Reflux Disease. (2025)

Byline: Yue. Qu, Jing-Ying. Ye, De-Min. Han, Li. Zheng, Xin. Cao,Yu-Huan. Zhang, Xiu. Ding

Background: Obstructive sleep apnea/hypopnea syndrome (OSAHS) andlaryngopharyngeal reflux (LPR) disease have a high comorbidity rate, butthe potential causal relation between the two diseases remains unclear.Our objectives were to investigate the esophageal functional changes inOSAHS patients and determine whether OSAHS affects LPR by affectingesophageal functions. Methods: Thirty-six OSAHS patients and 10 healthycontrols underwent 24-h double-probed combined esophageal multichannelintraluminal impedance and pH monitoring simultaneously withpolysomnography. High-resolution impedance manometry was applied toobtain a detailed evaluation of pharyngeal and esophageal motility.Results: There were 13 OSAHS patients (36.1%) without LPR (OSAHS group)and 23 (63.9%) with both OSAHS and LPR (OSAHS and LPR group).Significant differences were found in the onset velocity of liquidswallows (OVL, P = 0.029) and the percent relaxation of the loweresophageal sphincter (LES) during viscous swallows (P = 0.049) betweenthe OSAHS and control groups. The percent relaxation of LES duringviscous swallows was found to be negatively correlated with uprightdistal acid percent time (P = 0.016, R = −0.507), and OVL wasfound to be negatively correlated with recumbent distal acid percenttime (P = 0.006, R = −0.557) in the OSAHS and LPR group.Conclusions: OSAHS patients experience esophageal functional changes,and linear correlations were found between the changed esophagealfunctional parameters and reflux indicators, which might be the reasonthat LPR showed a high comorbidity with OSAHS and why the severity ofthe two diseases is correlated.

Introduction

Obstructive sleep apnea/hypopnea syndrome (OSAHS) is characterizedby repetitive upper-airway collapse during sleep, causing sleepfragmentation, oxygen desaturation, and daytime sleepiness.[sup][1],[2]Approximately, 2–5% of the population are affected by OSAHSproblems.[sup][2] Two factors that are generally accepted to have aneffect on OSAHS are upper-airway muscular hypotonia (from neuromusculardiseases or toxic reactions) and abnormal anatomical narrowing.[sup][3]Many systemic diseases, such as congestive heart failure,cerebrovascular incidents, and metabolism syndrome, are demonstrated tobe related to this syndrome.[sup][2],[4],[5] OSAHS has also become avital issue leading to automobile accidents.[sup][6]

Adopted by the American Academy of Otolaryngology – Headand Neck Surgery in 2002, laryngopharyngeal reflux (LPR) is the backflowof gastric contents to the laryngopharynx and upper aerodigestivetract.[sup][4],[7] LPR was believed to be extraesophageal manifestationsof gastroesophageal reflux disease (GERD),[sup][8] causing hoarseness,globus, dysphagia, cough/throat clearing, and excessive throat mucus.LPR affects 4–10% of patients in otolaryngology.[sup][9]

Both OSAHS and LPR are extremely harmful to human health, and thecoexistence of the two diseases is 45.4%;[sup][2] however, the potentialcausal relation between the two diseases remains under debate. It hasbeen reported that OSAHS patients have more reflux events than thehealthy controls, and continuous positive airway pressure therapy canreduce the occurrence of nocturnal reflux events,[sup][10],[11] but noexplicit correlation was found between reflux events and apnea.[sup][12]Our team also found a correlation between the severity of OSAHS andreflux, but no clear corresponding relation was found between refluxevents and apnea.[sup][13],[14]

It was proved that chronic neuromuscular injury exists in thegenioglossus muscle of OSAHS patients, and reduction in the activity ofthe upper-airway dilators contribute to OSAHS development.[sup][3],[15]In addition, esophageal motility abnormalities are among the mainfactors implicated in the pathogenesis of GERD.[sup][16] Our aims forthis study were to investigate the esophageal functional changes inOSAHS patients and determine whether OSAHS affects LPR by affectingesophageal functions.

Methods

Subjects and study design

This study was conducted at Department of Otolaryngology, BeijingTongren Hospital, China, between January 2011 and December 2014. Signedinformed consent was received from all study participants, and the studyprotocol was approved by the ethics committee of the hospital.

Ten healthy volunteers (mean age 45 [+ or -] 4 years, 5 females)and 36 OSAHS patients (mean age 47 [+ or -] 2 years, 5 females) wereenrolled in this study. All healthy volunteers were between 18 and 70years old and none had any snoring issues or LPR symptoms, such ashoarseness, dysphagia, globus, regurgitation, heartburn, cough/throatclearing, or excessive throat mucus, within 2 months of the study orexperienced these conditions only very mildly. All OSAHS patients alsoranged in age from 18 to 70 years and had symptoms of apnea and daytimesleepiness. Patients with a history of severe systemic diseases,laryngopharyngeal surgery, or hiatal hernia were excluded from thestudy. Those who had received any treatments for OSAHS or LPR were alsoexcluded.

The medical history of all participants was carefully recorded byone ENT doctor to obtain a reflux symptom index.[sup][17] A completeendoscopic examination of the upper-airway was performed by the same ENTdoctor while the reflux finding scores of the patients weredetermined.[sup][2],[18] High-resolution impedance manometry was used toobtain a detailed evaluation of pharyngeal and esophageal motility, andthe location of the upper esophageal sphincter (UES), and the loweresophageal sphincter (LES). All patients underwent polysomnography (PSG)testing on the same night with double-probed 24-h combined esophagealmultichannel intraluminal impedance and pH (MII-pH) monitoring.

Patients with OSAHS were divided into two groups according to the24-h MII-pH monitoring as follows: OSAHS only and both OSAHS and LPR(OSAHS and LPR). Eighty-four esophageal functional indicators werecompared among the OSAHS groups and the control. Correlations weretested between the selected esophageal functional indicators and refluxparameters in the OSAHS and LPR group.

Esophageal function testing

High-resolution impedance manometry using the Sandhill esophagealfunction test (EFT) catheter 38-channel probe (Sandhill Scientific Inc.,Highlands Ranch, CO, USA) was inserted into all study participants afteran overnight fast for an EFT. The 4.5 mm – diameter catheterhas 32 circumferential solid-state pressure sensors spaced at 1.0-cmintervals. Impedance measuring segments consisted of two metal ringsplaced 2.0 cm apart, centered at 10, 15, 20, and 25 cm from the tip[Figure 1]. The catheter was put into the esophagus passing through thenose to a depth of 60 cm. It was then pulled slowly upward until themost distal sensor was seated in the high-pressure zone of LES. Theintraesophageal pressure sensors and impedance measuring segments weresubsequently located 5 (distal), 10 (midway 2), 15 (midway 1), and 20(proximal) cm above LES. Following at least a 30-s baseline reading toidentify UES and LES, 105.0-ml saline and 105.0-ml viscous swallows atleast 30 s apart were performed with the patient in a supine position.The esophageal functional indicators of saline and viscous swallows wereanalyzed separately.{Figure 1}

Ambulatory pH monitoring

Ambulatory 24-h MII-pH monitoring was applied to all participantsusing a ZepHr recorder and the Sandhill ZAI-BL-48E double-probedcatheter (Sandhill Scientific Inc., Highlands Ranch, CO, USA). Eachprobe carried one antimony pH electrode and several impedanceelectrodes. Each pair of adjacent electrodes represents animpedance-measuring segment (2.0 cm long). EFT was performed beforeMII-pH monitoring to detect the locations of LES and UES. A pharyngealprobe was placed 1 cm above the superior border of UES, and theesophageal probe was placed 5 cm above LES through the nose. Data werestored in a portable receiver with an impedance amplifier. Participantswere required to record their meals, body position changes, and anysymptoms.

LPR was considered to be positive when at least one of thefollowing criteria was met:[sup][19] (1) Total acid exposure time (%)>0.1%, (2) acid exposure time (%) in upright position >0.2%, (3)acid exposure time (%) in supine position >0.0%, and (4) acid refluxnumber ≥4.

Polysomnography

All the participants underwent diagnostic sleep studies during the24-h MII-pH monitoring period using an ambulatory Emblata S4000 recorder(SASN Medical Supplies Co., Ltd., China). Nasal airflow, oxyhemoglobinsaturation, body position, and thoracic and abdominal movements wererecorded overnight. Apnea episodes were defined as complete cessation ofairflow lasting at least 10 s. Hypopnea was defined as at least a 50%reduction in airflow for at least 10 s accompanied by a reduction inSO[sub]2 of at least 4%. AHI was defined as the number of events ofapnea or hypopnea per hour during sleep time based on the results of theovernight PSG. The participants with an AHI ≥5 events/h andwith associated symptoms were considered to be OSAS-positive cases,according to the American Association of Sleep Medicinecriteria.[sup][1]

Statistical analyses

Statistical analyses were performed using SPSS 20.0 (IBMCorporation, Chicago, IL, USA). Data having a normal distribution werepresented as the mean [+ or -] standard deviation (SD). The data havingnonnormal distribution were presented as the median (M) and the 25% and75% percentiles (P25, P75). For normally distributed data, independent t-tests were used to compare the esophageal functional parameters amongthe OSAHS groups and the control and one-way analysis of variance(ANOVA) was used to compare the normally distributed parameters amongthe three groups. For data in nonnormal distribution, theMann–Whitney U -test was used to compare the differences amongthe groups. Pearson's coefficient and Spearman's coefficientwere used to analyze the associations between normally distributed andnonnormally distributed variables of interest with reflux indicators,respectively. P < 0.05 was considered to be statisticallysignificant.

Results

Demographics and characteristics

Thirteen patients were diagnosed with having only OSAHS (49 [+ or-] 2 years old, 1 female), and 23 patients were diagnosed with havingboth OSAHS and LPR (46 [+ or -] 2 years old, 4 females). The demographiccharacteristics, main PSG, and reflux indicators of the participants areprovided in [Table 1]. No significant differences were found in the meanages among the three groups. The body mass index (BMI) in the OSAHS andLPR disease group was significantly higher than that in the control ( P= 0.01).{Table 1}

Esophageal functional parameters

Eighty-four esophageal functional parameters were compared betweenthe OSHAS group and the control. To exclude the impact of LPR, theesophageal functional indicators were compared between the patients withOSAHS only and the control instead of all 36 OSAHS patients and thecontrol. [Table 2] shows the comparison of some main indicators ofesophageal function in the healthy controls and the OSAHS patients.Other parameters of esophageal function were also compared, but nosignificant differences were found.{Table 2}

Correlation between esophageal function and reflux parameters

Correlations were tested between the indicators selected above andthe indicators for reflux severity in patients in the OSAHS and LPRgroup. Significant correlations were found among these parameters andsome of the reflux indicators. [Table 3] shows the correlation among theselected parameters and the severity of reflux in the OSAHS and LPRgroup. [Figure 2] shows the correlation between onset velocity of liquid(OVL) swallows and the percent time of recumbent distal acid episodes.[Figure 3] shows the correlation between LES percent relaxation ofviscous swallows and the longest upright distal acid episodes.{Table3}{Figure 2}{Figure 3}

Correlation between esophageal function and obstructive sleepapnea/hypopnea syndrome severity

Correlations were tested between OSAHS severity and the selectedesophageal functional parameters in the OSAHS group and the OSAHS andLPR group; however, no significant correlations were found between theseverity of OSAHS and the changed esophageal functional indicators.[Table 4] shows the correlations between OSAHS severity and esophagealfunction in the OSAHS group. The correlations between OSAHS severity andesophageal functions in the OSAHS and LPR group are provided in [Table3].{Table 4}

Polysomnography parameters

Polysomnography parameters were compared between the OSAHS andOSAHS and LPR groups. The percentage of time with oxygen saturationbelow 90% was significantly different between the OSAHS and OSAHS andLPR groups; however, there were no significant differences in otherOSAHS severity indicators between the two groups. [Table 5] shows thecomparison of PSG parameters between both groups.{Table 5}

Discussion

This study focused mainly on the potential correlation betweenOSAHS and LPR in esophageal function. We found that some of theesophageal functional parameters were significantly different betweenOSAHS patients and the controls and were significantly correlated withsome of the reflux parameters when OSAHS and LPR coexisted.

Researchers have pointed out that OSAHS has a high comorbidity withLPR;[sup][2] however, the relation between OSAHS and LPR remains underdebate. It was found that there were certain consistencies between theseverity of reflux and OSAHS based on a questionnaire,[sup][20] whereasstudies have not shown a direct temporal link between apneic and LPRevents.[sup][13] Mechanisms by which the two diseases are associatedinclude large negative intrathoracic pressure swings generated duringobstructive apneas and respiratory-related arousals, which appear to beassociated with LES relaxation, and laryngeal sensorydysfunction.[sup][10],[12],[21] It has been reported that the prevalenceof LPR among OSAHS patients is higher than that in the generalpopulation.[sup][2],[9],[14] Our study had similar findings. A 63.9% LPRcoexist rate was found among patients with snoring problems.

Given that upper-airway muscular hypotonia exists in OSAHSpatients,[sup][3],[15] and esophageal motility abnormalities were foundin reflux diseases,[sup][8],[16] we suspect that OSAHS patients mighthave esophageal functional disorders, which might be the reason that LPRshowed a high comorbidity with OSAHS, and esophageal function might beone of the points that join the two diseases together. Kuribayashi et al.[sup][10] simultaneously applied high-resolution manometry, impedanceand pH recordings, and PSG to 26 patients with OSAHS and/or GERD toobtain the pressure changes in UES and the gastroesophageal junctionduring apneic periods, but the transmission and clearance functions ofthe esophagus were not measured.

In this research, the OVL swallows was found significantlydifferent between the healthy control and OSAHS groups. Calculated fromthe two most distal analysis channels, the OVL swallows is an indicatorfor the distal esophageal contraction.[sup][22] Although this parametercould be accepted as normal in OSAHS patients, the two diseased groupsappeared to have an OVL lower than that of the healthy control. Inaddition, OVL showed a linear relation with some of the refluxindicators that appears to prevent reflux in the patients with both LPRand OSAHS. Similarly, LES percent relaxation of viscous swallows wasfound significantly different between OSAHS patients and healthy peopleand was also found correlated with some of the reflux parameters whenOSAHS and LPR coexist. These results revealed that esophageal functionalchanges exist in OSAHS patients, and some of the changed esophagealfunctional parameters are correlated with reflux indicators in patientswith both OSAHS and LPR. This might explain why the occurrence of LPR inOSAHS patients is high, and why the severity of the two diseases iscorrelated; however, the changed parameters were considered to be normalaccording to the normal range. In addition, individual differences existamong OSAHS patients. In our study, BMI was significantly higher in theOSAHS and LPR group than in the OSAHS and control groups. However, BMIshowed no correlation with the changed esophageal functional parameters.

To our knowledge, the esophageal functional changes and the reasonthat they changed in OSAHS patients remain unclear, but it has beenproved that the upper-airway dilator dysfunction exists in OSAHSpatients.[sup][3] Upper-airway dilators are mainly innervated by thepharyngeal branch of vagus and trigeminal nerves. Composed of thecricopharyngeus and inferior pharyngeal constrictor, UES is mainlyinnervated by the glossopharyngeal nerve and branches of the vagus andaccessory nerves,[sup][23] and LES is innervated by the enteric nervoussystem of the vagus nerve.[sup][24] Thus, the upper-airway dilators andthe esophageal sphincters are affected by the vagus nerve and mightshare the same regulatory mechanisms. Repeated apnea, oxygendesaturation, and sleep fragmentation during sleep might cause autonomicdysfunction,[sup][25] which might impact vagus nerve function andsubsequently, impact esophageal functions. Further researches are neededto reveal the mechanism by which the function or dysfunction of thevagus nerve influences the function of the esophageal sphincter.

This study was limited by sample size. Additional larger, long-termstudies are needed to determine whether a causal relationship existsbetween the two diseases. There are also several deficiencies in thisstudy. First, sex differences were not excluded in this study. Becausewe had female patients with OSAHS, we also enrolled female volunteersinto the control group.

In conclusion, obstructive sleep apnea/hypopnea syndrome patientsexhibit esophageal functional changes, which might be why LPR showed ahigh comorbidity with OSAHS. Linear correlations were found between someof the changed esophageal functional parameters and reflux indicators,which might explain why the severity of these two diseases iscorrelated.

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