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Original Research: SLEEP MEDICINE |

The Effect of 1 Week of Continuous Positive Airway Pressure Treatment in Obstructive Sleep Apnea Patients With Concomitant Gastroesophageal Reflux* FREE TO VIEW

Maroun Tawk, MD, FCCP; Suanne Goodrich, PhD; Gary Kinasewitz, MD, FCCP; William Orr, PhD
Author and Funding Information

*From Pulmonary and Critical Care Medicine (Drs. Tawk and Kinasewitz), University of Oklahoma Health Sciences Center; and Lynn Institute Sleep Laboratory (Drs. Goodrich and Orr), Lynn Health Science Institute, Oklahoma City, OK.

Correspondence to: Maroun M. Tawk, MD, FCCP, 920 Stanton L. Young Blvd, WP 1310, Oklahoma City, OK 73104; e-mail: Maroun-tawk@ouhsc.edu



Chest. 2006;130(4):1003-1008. doi:10.1378/chest.130.4.1003
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Study objectives: Patients with obstructive sleep apnea (OSA) have a very high incidence of gastroesophageal reflux (GER). Previous studies have shown that the use of continuous positive airway pressure (CPAP) reduces the frequency of reflux events, but these studies only assessed the effect of a single night of treatment. The aim of this study was to assess the effect of 1 week of CPAP treatment on reflux in patients with OSA and GER.

Design: Sixteen patients with OSA and GER were recruited. Polysomnography followed by 24-h, continuous esophageal pH monitoring were performed at baseline. Patients with an apnea-hypopnea index (AHI) > 20/h and 24-h acid contact time (ACT) of at least 6% were included. As part of the polysomnography-qualifying evaluation, all patients underwent CPAP titration to reduce the AHI to < 10/h. Patients were then sent home receiving nasal CPAP for 1 week; after 1 week, esophageal pH monitoring was repeated while receiving CPAP.

Measurements and results: The AHI fell from 63.3 ± 38.5 to 3.2 ± 2.2/h (mean ± SD) [p < 0.001]. Total ACT fell from 13.9 ± 11.6 to 5.6 ± 2.7% (p < 0.001). The upright ACT was reduced from 12.4 ± 6.8 to 6.8 ± 3.8% (p = 0.01), and the supine (during the sleeping interval) ACT was reduced from 16.3 ± 18.8 to 3.8 ± 7.6% (p < 0.01). Eighty-one percent of the patients had a reduction in supine ACT to within the normal range (< 4%).

Conclusions: In OSA patients with significant heartburn complaints, CPAP would appear to be an efficacious approach to the treatment of both disorders.

Figures in this Article

Obstructive sleep apnea (OSA) is a common abnormality, occurring in approximately 4% of adult men and 2% of adult women.1The incidence rises with obesity and increasing age.2Several studies have examined the relationship between actual obstructive apneic events and the occurrence of gastroesophageal reflux (GER). In one study,380% of the patients with OSA had abnormal esophageal acid contact time (ACT) with > 4% of the ACT spent at pH < 4. Continuous positive airway pressure (CPAP) delivered via a nasal or full face mask is the cornerstone of OSA therapy. CPAP is thought to work by stenting the upper airway open and preventing its collapse during sleep. Previous reports46 in the literature have indicated that the acute administration of CPAP reduces the occurrence of GER in patients with OSA. However, these studies evaluated only an acute response for a single night of CPAP treatment, and the persistence of this response has never been evaluated. We hypothesized that the beneficial effect of CPAP therapy on GER in OSA patients would be maintained if CPAP use were continued. To examine this hypothesis, we assessed the effect of 1 week of CPAP therapy on nocturnal and daytime esophageal reflux in patients with documented moderate-to-severe OSA and GER.

Subjects

The protocol was reviewed and approved by the Institutional Review Board at The University of Oklahoma Health Sciences Center. Appropriate informed consent was obtained from all patients. Patients were identified as likely to have sleep apnea based on clinical criteria including loud snoring, interrupted sleep at night, and excessive daytime sleepiness. Patients were required to have symptoms of reflux for at least 4 days a week, and awakening from sleep with heartburn at least once a week. The study design is illustrated in Figure 1 .

Baseline Study

All patients underwent initial polysomnography to determine the presence of a baseline rate of obstructive events defined as an apnea-hypopnea index (AHI) of at least 20 events per hour. This polysomnography was performed as a standard split-night study during which the patient was monitored for a minimum of 2 h of sleep to determine the baseline AHI. This was followed by a CPAP titration to reduce the obstructive events to < 10/h. On the day following the sleep study, patients underwent a 24-h esophageal pH evaluation starting at 4 pm as described below. All patients were asked to stop their histamine type-2 blockers and/or proton-pump inhibitors for a week prior to enrollment and for the duration of the study.

Intervention

Patients with an AHI > 20/h and an esophageal ACT of at least 6% were sent home with a CPAP machine after instruction in the setup and use of the equipment. These individuals then received 1 week of CPAP treatment at the optimal therapeutic level as determined in the initial polysomnography.

Follow-up Evaluation:

After approximately 7 nights of CPAP treatment, repeat 24-h esophageal pH monitoring and polysomnography were performed (Fig 1). This evaluation occurred with CPAP treatment and concomitant esophageal pH monitoring. Again, the pH study began at 4 pm on the night of polysomnography for consistency.

Polysomnography

Polysomnography included a standard EEG, electrooculogram, and submental electromyogram monitoring for sleep staging. Respirations were monitored using chest and abdominal impedance plethysmography. Airflow was assessed with a nasal pressure cannula. Arterial oxygen saturation was monitored with continuous pulse oximetry. Heart rate and rhythm were recorded and monitored with continuous ECG. Periodic limb movements were monitored using bilateral tibial electromyograph leads. All polysomnographies were administered and scored by experienced sleep laboratory technicians. Apnea was defined as a complete cessation of airflow lasting ≥ 10 s. Hypopnea was defined as reduction in respiratory airflow > 30%, lasting ≥ 10 s, and accompanied by a decrease ≥ 3% in oxygen saturation and/or an arousal. The AHI was defined as the number of apneas and hypopneas per hour of sleep and was used to diagnose OSA. Arousals were defined according to the recommendations of the American Sleep Disorders Association Atlas task force.7Sleep data were staged according to the system of Rechtschaffen and Kales.8

24-h pH Recording

Standardized methods of esophageal manometry and ambulatory 24-h esophageal pH testing were employed. After an overnight fast, the lower esophageal sphincter (LES) was located via esophageal manometry utilizing a standard nasal catheter with three solid state transducers (Sandhill Scientific; Littleton, CO). A 2.5-mm diameter catheter with two antimony pH electrodes was passed nasally and positioned with the distal electrode 5 cm above the cephalad border of the LES. The position was noted, and the electrodes were placed in the same position, but manometry was not performed on follow-up study to minimize discomfort to the patient. The electrodes were calibrated at pH 7 and pH 1 using a buffer solution before and at the completion of each study. A reference electrode was placed on the anterior chest. Electrodes were connected to a portable data storage device that stored pH data every 5 s (Medtronics; Minneapolis, MN; or Sandhill Scientific). Subjects went home with instructions to record meal times, time of assuming the supine position for sleep, and time of arising in the morning. Subjects were encouraged to perform normal daily activities. Subjects were instructed to report symptoms in a diary and to push the event button on the whenever they had relevant symptoms.

After 24 h of recording, data were downloaded and analysis was performed, which included the measurement over the total 24 h as well as in the upright (during waking) and supine (during the sleeping interval) positions. The following parameters were calculated: (1) percentage of esophageal ACT calculated as the duration in minutes the esophageal pH was < 4.0 divided by the total recording time × 100; (2) total number of reflux events for the total recording interval; (3) number of reflux events lasting > 5 min; (4) mean duration of reflux events; and (5) mean duration of the longest reflux event.

Statistical Analysis

Summary statistics are presented for each of the response variables at baseline and at end of treatment. Data are presented as mean ± SD. The efficacy of the treatment was based on the magnitude of the reduction of these variables by the week-long treatment. Initially, paired t tests were conducted to test for differences on the dependent measures before and after CPAP treatment. Many variables were not normally distributed, however, so the Wilcoxon signed-rank test was performed on all variables instead. The results of the paired t tests and Wilcoxon ranked-sum test were almost identical, but the Wilcoxon ranked-sum results will be reported here.

Forty-three patients were screened, and 16 patients (14 men and 2 women) were enrolled in the study. The others were excluded either because of AHI < 20/h (n = 13) or because of 24-h ACT < 6% (n = 11). Two patients were excluded because of very severe sleep apnea associated with significant oxygen desaturation that required supplemental oxygen during the night. The average use of CPAP was 5.9 ± 1.7/h per night. The mean body mass index (BMI) was 35.1 ± 6.6 kg/m2 (Table 1 ).

Effect of CPAP on OSA and GER

Overall, the study group had severe sleep apnea with significant improvement after CPAP. The average AHI was reduced from 63.3 ± 38.5 to 3.2 ± 2.2/h (p < 0.001). Results of the CPAP treatment for total percentage of ACT are presented in Figure 2 . It can be seen that there was a significant decline in esophageal ACT. Results for the upright (waking subsequent to the CPAP treatment night) and supine position are presented in (Fig 3, 4 ). Again, ACT was significantly reduced not only during the nighttime with CPAP administration, but also in the upright posture during the subsequent waking time during the day. The number of reflux events in the upright and supine positions also showed a significant decline with CPAP treatment as did the duration of the longest event (Figs 567 ).

Eighty-one percent of the patients had a reduction in supine ACT to within the normal range (< 4%), and 56% had a reduction of the upright ACT to < 8%. The average duration of longest reflux event was reduced to 12.4 ± 13.8 min (p < 0.01) [Fig 7]. The sleep architecture was improved with a decrease in the mean total arousal index from 19.7 ± 22 to10.2 ± 8.3/h (p = 0.05).

To our knowledge, this is the first study that has examined the effect of CPAP on GER in patients with sleep apnea beyond 1 single night of therapy. We found a significant reduction in the total 24-h acid contact. This was more impressive in the supine position when the patient was receiving CPAP. To our surprise, this beneficial effect was maintained to a certain extent during the day when the patient was awake and not receiving CPAP.

The coexistence of OSA and GER is common in the obese patient. Several studies have examined the relationship between actual obstructive apneic events and the occurrence of GER. In a large epidemiologic survey done in three European countries, Janson et al9 showed that patients with symptoms of nighttime heartburn at least 1 night per week had an odds ratio with snoring of 2.75. Graf et al3found that 80% of the patients with OSA had abnormal ACT. Ing and colleagues4 studied 63 patients with polysomnography-documented OSA (mean AHI > 40/h) compared to a group of control subjects without OSA with regard to the simultaneous occurrence of obstructive events and GER as monitored by esophageal pH. Patients and control subjects were matched for age, lung function, BMI, and alcohol intake. They found that patients with OSA had significantly more GER events than control subjects (21.4% vs 3.7% of time spent at esophageal pH < 4; p < 0.001).4

It is postulated that the supine position, the frequent arousals from sleep, and the extreme negative intrathoracic pressures created by respiratory effort in the face of upper airway obstruction in patients with OSA all act in concert to increase the risk for the occurrence of nocturnal GER and its attendant complications. In addition obesity, by enhancing the pressure gradient via increased intraabdominal pressure and displacing the stomach cephalad would be yet another putative risk. However, the relationship between body mass, OSA, and GER is more complex and not completely understood since nocturnal GER has been observed in obese patients with and without OSA. In patients with OSA and GER, Kerr et al5 were able to demonstrate that arousal, movement, and swallowing were more frequent (p < 0.043) in the 30 s prior to precipitous drops in esophageal pH than during random control periods. Also, a study by Freiden and colleagues10 demonstrated that GER events occurring during sleep occurred primarily associated with brief arousal responses. This temporal relationship was not confirmed in subsequent studies. Graf et al3classified 17 patients with proven OSA into two groups according to the severity of OSA: (1) with apnea index > 5/h and < 15/h (n = 8); and (2) with apnea index > 15 (n = 9). All patients underwent 24-h pH monitoring in the proximal and distal esophagus and simultaneous apnea monitoring during the night. There was no significant difference between the two groups with respect to reflux time at the distal or proximal esophageal site. Also the timing of the reflux episodes and the apnea periods were not correlated. In the same context, Ing and colleagues4 found that the correlation between OSA and GER was weak since only 53.4% of GER episodes were temporally related to apneas or hypopneas and 46.8% of all apneas were temporally related to acid reflux.4 Thus, it appears that a direct relationship between an obstructive event and an episode of GER cannot be established.

CPAP is the cornerstone of OSA therapy. It has been shown that the acute administration of CPAP reduces the occurrence of GER. The first case report on the effect of CPAP on “nocturnal reflux” in patients with OSA came from Diaz et al,6 who briefly reported the successful treatment of five patients with OSA complaining of severe refractory reflux esophagitis with the use of CPAP.6 In 1992, Kerr et al5 performed 2 consecutive days of 24-h esophageal monitoring, nocturnal esophageal pressure recording, and polysomnography on six OSA patients complaining of regular nocturnal GER. Baseline data were recorded on the first night. Nasal CPAP was administered on the second night and successfully treated apneas in five of six patients. Kerr et al5 noticed a dramatic reduction in GER frequency and duration. The beneficial effect of nasal CPAP on GER is not exclusive to patients with OSA but was also demonstrated in patients without sleep apnea. Kerr at al11 studied the acute effect of 8 cm H2O of CPAP on six non-OSA patients with significant GER (ACT > 5%). After application of CPAP, there was significant improvement in the reflux parameters including the 24-h ACT (27.7 to 10%), the mean reflux duration (2.1 to 0.9 min), and the mean length of the longest reflux episode (84.3 to 13.8 min).,11Shoenut et al12 also demonstrated that CPAP was effective in reducing GER in six non-OSA (scleroderma and achalasia) patients who had abnormal esophageal motility and resting LES pressure. They found that nasal CPAP administered acutely reduced the frequency and duration of nocturnal reflux in patients with achalasia, but not in patients with scleroderma.

In our study, we demonstrated that CPAP for patients with significant sleep apnea (AHI > 20/h) continues to have a beneficial effect on nocturnal GER after 1 week of therapy. The cutoff of 20 events per hour for AHI was chosen in order to ensure we involved patients with significant OSA. Clinically, this would be considered mild-to-moderate OSA. The period of 7 days was chosen to ensure compliance with CPAP intervention and follow-up. Patients were encouraged to maintain a normal life and not to modify their diet, which was confirmed by reviewing their daily log. Finally, there was no significant change in the body weight because of the short time interval between the initial and repeat evaluation.

The mechanism by which CPAP reduces the prevalence of GER is speculative. CPAP can elevate intrathoracic pressure by reducing airway obstruction and inspiratory effort, and by transmission of positive pressure to the intrathoracic airways. By raising intraesophageal pressure, the risk of GER should be reduced in patients with OSA regardless of the reflux mechanism involved. Other potential mechanisms are an increase in LES pressure by reflex mechanisms or direct mechanical compression of the mid-esophagus.13 Alternatively, a reduction of arousal and movement frequency in OSA patients may be responsible for the reduction in reflux events.11 The relative importance of these different mechanisms in the reduction of GER in patients receiving nasal CPAP needs to be investigated in future studies. The extended beneficial effect of the CPAP on daytime GER was unexpected. This finding was substantial and needs to be replicated by future research.

Our study has several limitations. First, there was no control group with sham CPAP. We believed that it would not be ethical to withhold therapy from patients with significant sleep apnea and excessive daytime sleepiness. Second, the two esophageal pH evaluations were performed under different conditions. The first test was done on an ambulatory basis, in which patients were sleeping in their own environment with full access to food. Although ambulatory during the day, the supine part of the second pH test was done in the sleep laboratory while patients were receiving CPAP. However, we feel that this difference is not likely to be of sufficient magnitude to substantially influence the results. The patients’ mobility during sleep was only minimally restrained since the monitoring was limited to the CPAP flow channel, and being the second night in the sleep laboratory the patients could be expected to be adapted to the laboratory conditions. Third, the patients’ eating habits might have changed during the study, which could have affected the results of the pH monitoring. To mimic conditions at home, all patients were offered a snack prior to the initiation of the second study. Finally, the pH probe per se may restrict the patient’s sleep position.14 Since this was the second pH test, we believe the previous experience with the pH probe may result in less disruption compared to the first 24-h pH study. Nonetheless, our findings are consistent with previous studies56,1112 suggesting that CPAP effects are not limited to an acute effect, but CPAP effects remain after 1 week of nightly treatment..

Abbreviations: ACT = acid contact time; AHI = apnea-hypopnea index; BMI = body mass index; CPAP = continuous positive airway pressure; GER = gastroesophageal reflux; LES = lower esophageal sphincter; OSA = obstructive sleep apnea

The authors have no conflicts of interest to disclose.

Figure Jump LinkFigure 1. Schematic of the experimental protocol. PSG = polysomnography.Grahic Jump Location
Table Graphic Jump Location
Table 1. Patient Demographics*
* 

Values are expressed as mean ± SD unless otherwise indicated.

Figure Jump LinkFigure 3. Effect of CPAP on ACT in supine position.Grahic Jump Location
Figure Jump LinkFigure 4. Effect of CPAP on ACT in the upright position.Grahic Jump Location
Figure Jump LinkFigure 5. Effect of CPAP on number of reflux events in the upright position.Grahic Jump Location
Figure Jump LinkFigure 6. Effect of CPAP on number of reflux events in the supine position.Grahic Jump Location
Figure Jump LinkFigure 7. Effect of CPAP on longest reflux event duration.Grahic Jump Location
Young, T, Palta, M, Dempsey, J, et al (1993) The occurrence of sleep-disordered breathing among middle-age adults.N Engl J Med328,1230-1235. [CrossRef] [PubMed]
 
Ancoli-Israel.. Epidemiology of sleep disorders.Clin Geriatr Med1989;5,347-362. [PubMed]
 
Graf, KI, Karaus, M, Heineman, S, et al Gastroesophageal reflux in patients with sleep apnea syndrome.Z Gastroenterol1995;33,689-693. [PubMed]
 
Ing, AJ, Ngu, MC, Breslin, AB Obstructive sleep apnea and gastroesphageal reflux.Am J Med2000;108,120-125. [PubMed]
 
Kerr, P, Shoenut, JP, Millar, T, et al Nasal CPAP reduces gastroesophageal reflux in obstructive sleep apnea syndrome.Chest1992;101,1539-1544. [CrossRef] [PubMed]
 
Diaz, S, Esteban, E, Piro, JM, et al Utility of CPAP in gastroesophageal reflux [letter]. Chest. 1990;;97 ,.:1275
 
American Sleep Disorders Association.. EEG arousals: scoring rules and examples; a preliminary report from the Sleep Disorders Atlas Task Force of the ASDA.Sleep1992;15,173-184. [PubMed]
 
Rechtschaffen, A, Kales, A. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. 1979; US Government Printing Office. Washington, DC: National Institutes of Health publication No. 204.
 
Janson, C, Gislason, T, De Backer, W, et al Daytime sleepiness, snoring and gastro-esophageal reflux amongst adults in three European countries.J Intern Med1995;237,277-285. [CrossRef] [PubMed]
 
Freidin, N, Fisher, J, Taylor, W, et al Sleep and nocturnal acid reflux in normal subjects and patients with reflux esophagitis.Gut1991;32,1275-1279. [CrossRef] [PubMed]
 
Kerr, P, Shoenut, JP, Streens, RD, et al Nasal continuous positive airway pressure: a new treatment for nocturnal gastroesophageal reflux?J Clin Gastroenterol1993;17,276-280. [CrossRef] [PubMed]
 
Shoenut, JP, Kerr, P, Micflicker, AB, et al The effect of nasal CPAP on nocturnal reflux in patients with aperistaltic esophagus.Chest1994;106,738-741. [CrossRef] [PubMed]
 
Fournier, MR, Kerr, P, Shoenut, JP, et al Effect of nasal continuous positive airway pressure on esophageal function.J Otolaryngol1999;28,142-144. [PubMed]
 
Fass, R, Hell, R, Sampliner, RE, et al Effect of ambulatory 24-hour esophageal pH monitoring on reflux-provoking activities.Dig Dis Sci1999;44,2263-2269. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Schematic of the experimental protocol. PSG = polysomnography.Grahic Jump Location
Figure Jump LinkFigure 3. Effect of CPAP on ACT in supine position.Grahic Jump Location
Figure Jump LinkFigure 4. Effect of CPAP on ACT in the upright position.Grahic Jump Location
Figure Jump LinkFigure 5. Effect of CPAP on number of reflux events in the upright position.Grahic Jump Location
Figure Jump LinkFigure 6. Effect of CPAP on number of reflux events in the supine position.Grahic Jump Location
Figure Jump LinkFigure 7. Effect of CPAP on longest reflux event duration.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Patient Demographics*
* 

Values are expressed as mean ± SD unless otherwise indicated.

References

Young, T, Palta, M, Dempsey, J, et al (1993) The occurrence of sleep-disordered breathing among middle-age adults.N Engl J Med328,1230-1235. [CrossRef] [PubMed]
 
Ancoli-Israel.. Epidemiology of sleep disorders.Clin Geriatr Med1989;5,347-362. [PubMed]
 
Graf, KI, Karaus, M, Heineman, S, et al Gastroesophageal reflux in patients with sleep apnea syndrome.Z Gastroenterol1995;33,689-693. [PubMed]
 
Ing, AJ, Ngu, MC, Breslin, AB Obstructive sleep apnea and gastroesphageal reflux.Am J Med2000;108,120-125. [PubMed]
 
Kerr, P, Shoenut, JP, Millar, T, et al Nasal CPAP reduces gastroesophageal reflux in obstructive sleep apnea syndrome.Chest1992;101,1539-1544. [CrossRef] [PubMed]
 
Diaz, S, Esteban, E, Piro, JM, et al Utility of CPAP in gastroesophageal reflux [letter]. Chest. 1990;;97 ,.:1275
 
American Sleep Disorders Association.. EEG arousals: scoring rules and examples; a preliminary report from the Sleep Disorders Atlas Task Force of the ASDA.Sleep1992;15,173-184. [PubMed]
 
Rechtschaffen, A, Kales, A. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. 1979; US Government Printing Office. Washington, DC: National Institutes of Health publication No. 204.
 
Janson, C, Gislason, T, De Backer, W, et al Daytime sleepiness, snoring and gastro-esophageal reflux amongst adults in three European countries.J Intern Med1995;237,277-285. [CrossRef] [PubMed]
 
Freidin, N, Fisher, J, Taylor, W, et al Sleep and nocturnal acid reflux in normal subjects and patients with reflux esophagitis.Gut1991;32,1275-1279. [CrossRef] [PubMed]
 
Kerr, P, Shoenut, JP, Streens, RD, et al Nasal continuous positive airway pressure: a new treatment for nocturnal gastroesophageal reflux?J Clin Gastroenterol1993;17,276-280. [CrossRef] [PubMed]
 
Shoenut, JP, Kerr, P, Micflicker, AB, et al The effect of nasal CPAP on nocturnal reflux in patients with aperistaltic esophagus.Chest1994;106,738-741. [CrossRef] [PubMed]
 
Fournier, MR, Kerr, P, Shoenut, JP, et al Effect of nasal continuous positive airway pressure on esophageal function.J Otolaryngol1999;28,142-144. [PubMed]
 
Fass, R, Hell, R, Sampliner, RE, et al Effect of ambulatory 24-hour esophageal pH monitoring on reflux-provoking activities.Dig Dis Sci1999;44,2263-2269. [CrossRef] [PubMed]
 
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