Scandinavian Journal of Gastroenterology. 2014; 49: 1035–1043
ORIGINAL ARTICLE
Endoscopic assessment of reflux esophagitis concurrent with hiatal hernia in male Japanese patients with obstructive sleep apnea
TAKAHIRO ZENDA1,2, KEI HAMAZAKI2, RIE OKA1, TOMOMI HAGISHITA1, SUSUMU MIYAMOTO1, JUNZO SHIMIZU3 & HIDEKUNI INADERA2 1
Department of Internal Medicine, Hokuriku Central Hospital of Japan Mutual Aid Association of Public School Teachers, Toyama, Japan, 2Department of Public Health, Faculty of Medicine, University of Toyama, Toyama, Japan, and 3Department of Thoracic Surgery, Hokuriku Central Hospital of Japan Mutual Aid Association of Public School Teachers, Toyama, Japan
Abstract Objective. The pathogenetic relationship underlying the high prevalence of gastroesophageal reflux disease (GERD) in patients with obstructive sleep apnea (OSA) remains unclear. In addition, GERD has not been adequately assessed by endoscopy in patients with OSA. The purpose of this study was to use endoscopy to investigate potential interactions among reflux esophagitis, hiatal hernia (HH) and OSA. Material and methods. A total of 243 consecutive male Japanese participants who underwent both overnight ambulatory polygraphic monitoring and esophagogastroduodenoscopy were retrospectively evaluated in a cross-sectional study. The prevalence and severity of HH and reflux esophagitis were assessed according to the Los Angeles classification and the Makuuchi classification, respectively. Associations among reflux esophagitis, HH and OSA were examined by univariate and multivariate analyses. Results. OSA was diagnosed in 98 individuals (40.3%). Endoscopy-confirmed esophagitis (p = 0.027) and HH (p < 0.001) were significantly more prevalent among patients with OSA. Multivariate regression model analysis adjusted for age, body mass index, visceral obesity represented by waist circumference, presence of OSA, concurrence of OSA and HH, smoking, and alcohol consumption yielded OSA as the only variable significantly associated with HH (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.35– 4.99; p = 0.004), while concurrence of OSA and HH was related to reflux esophagitis (OR, 3.59; CI, 1.87–6.92; p < 0.001). Conclusions. OSA was associated with HH and concurrent OSA and HH with reflux esophagitis in male Japanese patients with OSA. Our results support the hypothesis that complicating HH may link reflux esophagitis to OSA.
Key Words: endoscopy, gastroesophageal reflux disease, hiatal hernia, obstructive sleep apnea, reflux esophagitis
Introduction Obstructive sleep apnea (OSA) is defined as intermittent apnea or hypopnea during sleep due to obstruction or narrowing of the airway at the level of the oropharynx. Until airway patency is restored, labored inspiration against the progressive asphyxia produces a highly negative intrathoracic pressure and causes a brief arousal from sleep, which substantially fragments the sleep [1–5]. Besides its best-known manifestations, which include snoring and excessive daytime
somnolence, OSA induces a number of chronic health concerns related to the cardiovascular, cerebrovascular, pulmonary, digestive, metabolic, autonomic nervous and psycho-physiological systems [2–4]. Although many previous studies have demonstrated a higher prevalence of gastroesophageal reflux disease (GERD) among patients with OSA [6–11], the pathogenetic relationship between GERD and OSA remains controversial [1,4,7–12]. This is largely because OSA and GERD share many confounding factors such as obesity, middle to older age (>45
Correspondence: Takahiro Zenda, MD, Department of Internal Medicine, Hokuriku Central Hospital of Japan Mutual Aid Association of Public School Teachers, 123 Nodera, Oyabe, Toyama 932-8503, Japan. Tel: +81 766 67 1150. Fax: +81 766 68 2716. E-mail: [email protected]
(Received 18 February 2014; revised 11 May 2014; accepted 12 May 2014) ISSN 0036-5521 print/ISSN 1502-7708 online 2014 Informa Healthcare DOI: 10.3109/00365521.2014.926984
1036
T. Zenda et al.
Methods
examinations. The exclusion criteria were the use of proton pump inhibitors or histamine H2 receptor antagonists as gastric acid suppressants, use of hypnotic and/or psychotropic drugs, and lack of endoscopic images appropriate for evaluating reflux esophagitis and HH. No subject recruited had known gastrointestinal dysfunction, achalasia, scleroderma or history of surgery on the upper gastrointestinal tract. Alcohol consumption was defined as approximate total ethanol consumption per week of ‡150 g. Smoking was defined as habitual smoking at any time up until the time of this medical survey. The visceral adipose volume [25] and intra-abdominal pressure [16,17,26] were indirectly represented by the waist circumference (WC). Signed informed consent to participate was obtained from each subject, and the study protocol was reviewed and approved by the institutional ethics committees of Hokuriku Central Hospital (No. 3) and the University of Toyama (No. 24-103).
Study population
Anthropometry
Because Hokuriku Central Hospital provides comprehensive medical health surveys for members of the mutual aid association of public school teachers, current and retired teachers were enrolled consecutively as participants in this study. Among the individuals who underwent a medical health checkup program between September 2009 and September 2013, a total of 266 men (306 records) aged 29–79 years volunteered to undergo both overnight ambulatory polygraphic monitoring for diagnosis of OSA and upper gastrointestinal endoscopy. While candidates who underwent overnight ambulatory polygraphic monitoring were principally chosen on the basis of their OSA-suggestive symptoms (95.9%), those who underwent endoscopy were selected randomly. All participants were asked whether they had experienced symptoms suggestive of OSA (such as snoring, witnessed apnea or excessive daytime sleepiness) or GERD (such as heartburn, acid regurgitation, or pain or discomfort in the epigastric region) as well as about their histories of alcohol consumption, cigarette smoking, abdominal surgery, comorbid diseases and medication; these questions were based on the standardized questionnaire used in our institution. The subjects were limited to men because the prevalence rates of both OSA [7,14,17] and GERD [21,22,24] differ according to sex and because 17 of the number of patients with OSA out of 70 female participants were too small to support statistical analysis. Because lifestyle guidance regarding diet and exercise and/or treatments was immediately initiated in cases of OSA, the results of the first examination were used in each case regardless of the number of subsequent
The anthropometric measurements of the subjects were made in the morning by trained nurses. Weight was measured to the nearest 0.1 kg and was recorded after subtraction of 0.4 kg for the weight of the clothing. Height was measured with the subject either barefoot or wearing thin socks. Body mass index (BMI) was calculated by dividing the body weight (kg) by the square of the height (m2). WC was measured to the nearest 0.5 cm using a handheld measuring tape placed horizontally at the level of the navel as the participant exhaled quietly. The presence of kyphosis, which is well recognized as a critical predisposing factor for HH [12,22,27], was also evaluated.
years), male sex, smoking and alcohol consumption [3,4,6–16]. It is therefore unknown whether both diseases occur coincidentally on the same background or whether they are causally linked [4,7,13,17,18]. In previous studies, GERD has been evaluated principally on the basis of symptomatology questionnaires, pH-impedance reflux monitoring in the esophagus, esophageal manometry and endoscopy [4]. To date, there have been only two brief studies [4,19], in which GERD and hiatal hernia (HH), which is known to exacerbate GERD potently [4,13,15,17,20–23], were evaluated by endoscopy in patients with OSA. Our aim was to use endoscopy to assess the prevalence and severity of reflux esophagitis concomitant with HH in male Japanese patients with OSA and to analyze the results to investigate their potential interactions.
OSA evaluation Subjects underwent overnight portable polygraphic monitoring (LT-200, Fukuda Denshi Co., Ltd., Tokyo), which fulfills the Type 3 equipment [28,29] with five channels that measure nasal pressure via oronasal airflow, respiratory thoracic wall movement by the change in pressure in an air bag attached to the epigastrium, pulse oxygen saturation and pulse rate count via a finger probe, oropharyngeal vibration (16–70 Hz) to detect snoring, and body position. The measurements were first evaluated by computer analysis using the accompanying software (SAS-100) and then checked manually by the laboratory technicians to verify the apnea or hypopnea events according to the definitions issued by the American Academy of Sleep Medicine (AASM) in 2007 [30]. Apnea was defined as a ‡90% reduction in nasal airflow from the baseline amplitude (determined during the nearest
Association of OSA with hiatal hernia preceding period of regular breathing with stable oxygen saturation) lasting for ‡10 s. Hypopnea was defined as a >50% reduction from baseline in nasal airflow in association with ‡4% desaturation of arterial oxygen. The number of apnea and hypopnea events per hour of sleep was calculated as the apnea hypopnea index (AHI). All of the subjects slept for ‡6 h during the ambulatory polygraphic monitoring. Because Type 3 portable monitoring, despite several limitations, is accepted for OSA diagnosis in the 2007 AASM statement [28,29], and because recent studies using more simple portable monitoring (Type 4) also demonstrated good sensitivity and specificity relative to the gold standard method of polysomnography [29,31], subjects with an AHI of ‡5 points were conventionally diagnosed with OSA [2–4,6,7,9,10,18–20,32]. Subjects with an AHI score of 5 years of experience. The prevalence and severity of HH and reflux esophagitis were evaluated from the looking-down views. The severity of reflux esophagitis was judged according to the Los Angeles (LA) classification of Esophagitis system [33]: grade A, one or more mucosal breaks confined to the mucosal folds, each no longer than 5 mm; grade B, at least one ‡5-mm-long mucosal break confined to the mucosal folds but not continuous between the tops of two mucosal folds; grade C, at least one mucosal break continuous between the tops of ‡2 mucosal folds but not circumferential; and grade D, circumferential mucosal break. The severity of the HH was judged according to the Makuuchi classification [27]: grade A, definite HH (sac-shaped portion covered with gastric mucosa visible ‡3 cm above the hiatus); grade B, minor hernia (gastric mucosa visible circumferentially
ORIGINAL ARTICLE
Endoscopic assessment of reflux esophagitis concurrent with hiatal hernia in male Japanese patients with obstructive sleep apnea
TAKAHIRO ZENDA1,2, KEI HAMAZAKI2, RIE OKA1, TOMOMI HAGISHITA1, SUSUMU MIYAMOTO1, JUNZO SHIMIZU3 & HIDEKUNI INADERA2 1
Department of Internal Medicine, Hokuriku Central Hospital of Japan Mutual Aid Association of Public School Teachers, Toyama, Japan, 2Department of Public Health, Faculty of Medicine, University of Toyama, Toyama, Japan, and 3Department of Thoracic Surgery, Hokuriku Central Hospital of Japan Mutual Aid Association of Public School Teachers, Toyama, Japan
Abstract Objective. The pathogenetic relationship underlying the high prevalence of gastroesophageal reflux disease (GERD) in patients with obstructive sleep apnea (OSA) remains unclear. In addition, GERD has not been adequately assessed by endoscopy in patients with OSA. The purpose of this study was to use endoscopy to investigate potential interactions among reflux esophagitis, hiatal hernia (HH) and OSA. Material and methods. A total of 243 consecutive male Japanese participants who underwent both overnight ambulatory polygraphic monitoring and esophagogastroduodenoscopy were retrospectively evaluated in a cross-sectional study. The prevalence and severity of HH and reflux esophagitis were assessed according to the Los Angeles classification and the Makuuchi classification, respectively. Associations among reflux esophagitis, HH and OSA were examined by univariate and multivariate analyses. Results. OSA was diagnosed in 98 individuals (40.3%). Endoscopy-confirmed esophagitis (p = 0.027) and HH (p < 0.001) were significantly more prevalent among patients with OSA. Multivariate regression model analysis adjusted for age, body mass index, visceral obesity represented by waist circumference, presence of OSA, concurrence of OSA and HH, smoking, and alcohol consumption yielded OSA as the only variable significantly associated with HH (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.35– 4.99; p = 0.004), while concurrence of OSA and HH was related to reflux esophagitis (OR, 3.59; CI, 1.87–6.92; p < 0.001). Conclusions. OSA was associated with HH and concurrent OSA and HH with reflux esophagitis in male Japanese patients with OSA. Our results support the hypothesis that complicating HH may link reflux esophagitis to OSA.
Key Words: endoscopy, gastroesophageal reflux disease, hiatal hernia, obstructive sleep apnea, reflux esophagitis
Introduction Obstructive sleep apnea (OSA) is defined as intermittent apnea or hypopnea during sleep due to obstruction or narrowing of the airway at the level of the oropharynx. Until airway patency is restored, labored inspiration against the progressive asphyxia produces a highly negative intrathoracic pressure and causes a brief arousal from sleep, which substantially fragments the sleep [1–5]. Besides its best-known manifestations, which include snoring and excessive daytime
somnolence, OSA induces a number of chronic health concerns related to the cardiovascular, cerebrovascular, pulmonary, digestive, metabolic, autonomic nervous and psycho-physiological systems [2–4]. Although many previous studies have demonstrated a higher prevalence of gastroesophageal reflux disease (GERD) among patients with OSA [6–11], the pathogenetic relationship between GERD and OSA remains controversial [1,4,7–12]. This is largely because OSA and GERD share many confounding factors such as obesity, middle to older age (>45
Correspondence: Takahiro Zenda, MD, Department of Internal Medicine, Hokuriku Central Hospital of Japan Mutual Aid Association of Public School Teachers, 123 Nodera, Oyabe, Toyama 932-8503, Japan. Tel: +81 766 67 1150. Fax: +81 766 68 2716. E-mail: [email protected]
(Received 18 February 2014; revised 11 May 2014; accepted 12 May 2014) ISSN 0036-5521 print/ISSN 1502-7708 online 2014 Informa Healthcare DOI: 10.3109/00365521.2014.926984
1036
T. Zenda et al.
Methods
examinations. The exclusion criteria were the use of proton pump inhibitors or histamine H2 receptor antagonists as gastric acid suppressants, use of hypnotic and/or psychotropic drugs, and lack of endoscopic images appropriate for evaluating reflux esophagitis and HH. No subject recruited had known gastrointestinal dysfunction, achalasia, scleroderma or history of surgery on the upper gastrointestinal tract. Alcohol consumption was defined as approximate total ethanol consumption per week of ‡150 g. Smoking was defined as habitual smoking at any time up until the time of this medical survey. The visceral adipose volume [25] and intra-abdominal pressure [16,17,26] were indirectly represented by the waist circumference (WC). Signed informed consent to participate was obtained from each subject, and the study protocol was reviewed and approved by the institutional ethics committees of Hokuriku Central Hospital (No. 3) and the University of Toyama (No. 24-103).
Study population
Anthropometry
Because Hokuriku Central Hospital provides comprehensive medical health surveys for members of the mutual aid association of public school teachers, current and retired teachers were enrolled consecutively as participants in this study. Among the individuals who underwent a medical health checkup program between September 2009 and September 2013, a total of 266 men (306 records) aged 29–79 years volunteered to undergo both overnight ambulatory polygraphic monitoring for diagnosis of OSA and upper gastrointestinal endoscopy. While candidates who underwent overnight ambulatory polygraphic monitoring were principally chosen on the basis of their OSA-suggestive symptoms (95.9%), those who underwent endoscopy were selected randomly. All participants were asked whether they had experienced symptoms suggestive of OSA (such as snoring, witnessed apnea or excessive daytime sleepiness) or GERD (such as heartburn, acid regurgitation, or pain or discomfort in the epigastric region) as well as about their histories of alcohol consumption, cigarette smoking, abdominal surgery, comorbid diseases and medication; these questions were based on the standardized questionnaire used in our institution. The subjects were limited to men because the prevalence rates of both OSA [7,14,17] and GERD [21,22,24] differ according to sex and because 17 of the number of patients with OSA out of 70 female participants were too small to support statistical analysis. Because lifestyle guidance regarding diet and exercise and/or treatments was immediately initiated in cases of OSA, the results of the first examination were used in each case regardless of the number of subsequent
The anthropometric measurements of the subjects were made in the morning by trained nurses. Weight was measured to the nearest 0.1 kg and was recorded after subtraction of 0.4 kg for the weight of the clothing. Height was measured with the subject either barefoot or wearing thin socks. Body mass index (BMI) was calculated by dividing the body weight (kg) by the square of the height (m2). WC was measured to the nearest 0.5 cm using a handheld measuring tape placed horizontally at the level of the navel as the participant exhaled quietly. The presence of kyphosis, which is well recognized as a critical predisposing factor for HH [12,22,27], was also evaluated.
years), male sex, smoking and alcohol consumption [3,4,6–16]. It is therefore unknown whether both diseases occur coincidentally on the same background or whether they are causally linked [4,7,13,17,18]. In previous studies, GERD has been evaluated principally on the basis of symptomatology questionnaires, pH-impedance reflux monitoring in the esophagus, esophageal manometry and endoscopy [4]. To date, there have been only two brief studies [4,19], in which GERD and hiatal hernia (HH), which is known to exacerbate GERD potently [4,13,15,17,20–23], were evaluated by endoscopy in patients with OSA. Our aim was to use endoscopy to assess the prevalence and severity of reflux esophagitis concomitant with HH in male Japanese patients with OSA and to analyze the results to investigate their potential interactions.
OSA evaluation Subjects underwent overnight portable polygraphic monitoring (LT-200, Fukuda Denshi Co., Ltd., Tokyo), which fulfills the Type 3 equipment [28,29] with five channels that measure nasal pressure via oronasal airflow, respiratory thoracic wall movement by the change in pressure in an air bag attached to the epigastrium, pulse oxygen saturation and pulse rate count via a finger probe, oropharyngeal vibration (16–70 Hz) to detect snoring, and body position. The measurements were first evaluated by computer analysis using the accompanying software (SAS-100) and then checked manually by the laboratory technicians to verify the apnea or hypopnea events according to the definitions issued by the American Academy of Sleep Medicine (AASM) in 2007 [30]. Apnea was defined as a ‡90% reduction in nasal airflow from the baseline amplitude (determined during the nearest
Association of OSA with hiatal hernia preceding period of regular breathing with stable oxygen saturation) lasting for ‡10 s. Hypopnea was defined as a >50% reduction from baseline in nasal airflow in association with ‡4% desaturation of arterial oxygen. The number of apnea and hypopnea events per hour of sleep was calculated as the apnea hypopnea index (AHI). All of the subjects slept for ‡6 h during the ambulatory polygraphic monitoring. Because Type 3 portable monitoring, despite several limitations, is accepted for OSA diagnosis in the 2007 AASM statement [28,29], and because recent studies using more simple portable monitoring (Type 4) also demonstrated good sensitivity and specificity relative to the gold standard method of polysomnography [29,31], subjects with an AHI of ‡5 points were conventionally diagnosed with OSA [2–4,6,7,9,10,18–20,32]. Subjects with an AHI score of 5 years of experience. The prevalence and severity of HH and reflux esophagitis were evaluated from the looking-down views. The severity of reflux esophagitis was judged according to the Los Angeles (LA) classification of Esophagitis system [33]: grade A, one or more mucosal breaks confined to the mucosal folds, each no longer than 5 mm; grade B, at least one ‡5-mm-long mucosal break confined to the mucosal folds but not continuous between the tops of two mucosal folds; grade C, at least one mucosal break continuous between the tops of ‡2 mucosal folds but not circumferential; and grade D, circumferential mucosal break. The severity of the HH was judged according to the Makuuchi classification [27]: grade A, definite HH (sac-shaped portion covered with gastric mucosa visible ‡3 cm above the hiatus); grade B, minor hernia (gastric mucosa visible circumferentially
