This study was performed to explore high the prevalence of GERD in patients with OSA, which was found increased with age and severity of OSA. The possible reason is that the function of lower esophageal sphincter decreases across age. With age, lower esophageal sphincter tension decreases, gastric emptying is delayed, hiatal hernia easily appears, and esophageal clearance decreases.[23] The older the patient is, and the more likely it is the occurrence of reflux. A meta-analysis in South Korea from 2015 summarized seven studies on the prevalence of sleep disorders including OSA in patients with GERD. The study indicated that the prevalence of GERD ranges from 25.3–38.9% in patients with OSA.[9] Our study was consistent with the results of previous study. The endoscopic association of GERD with OSA was also demonstrated in a South Korean study in 2018, which demonstrated that decreased sleep quality was associated with GERD symptoms.[12] Our study is consistent with the study in that GERD is related to the severity of OSA. The high prevalence of GERD in OSA may be due to the common risk factors of the two diseases, such as obesity, smoking, and alcohol consumption.[24] At present, OSA and GERD are considered to interact as mutual influencers and aggravate each other. OSA leads to GERD mainly through the following mechanisms:(1) The swallowing reflex of patients with OSA is weakened, and the active esophageal peristalsis is reduced. In addition, when the patient is in the supine position, the esophageal clearance rate was significantly reduced. (2) When patients with OSA resume breathing after apnea, they need to overcome the obstructed upper airway and this can cause a significant decrease in intrathoracic pressure, an increase in septal pressure, and increase the risk of gastroesophageal reflux. Further, when respiratory tract obstruction occurs, cough is often caused by a reflex, which increases pressure in the abdominal cavity and aggravates the risk of gastroesophageal reflux.[25] (3) Patients with OSA frequently wake up at night, and this can trigger transient lower esophageal sphincter relaxation, causing and aggravating gastroesophageal reflux.[26] (4) The duration and recovery time of the lower esophageal sphincter (LES) and upper esophageal sphincter (UES) in patients with OSA are significantly lower than those in healthy individuals. Patients with OSA have anatomical abnormalities of the LES, which cannot guarantee an anti-reflux defense function, thus aggravating the occurrence of GERD. This study showed that the prevalence of GERD in patients with OSA is significantly correlated with the severity of OSA. The higher the number of AHI events, the higher the prevalence of GERD. A possible reason for this is that LES function gradually de-creases with age. When intra-abdominal pressure increases, reflux is more likely to occur and GERD may aggravate or cause OSA.[13]
In addition to reporting increased prevalence of GERD in OSA, previous studies have revealed a significant increase in the prevalence of OSA in patients with GERD. A 2014 study confirmed that patients with GERD and Barrett's esophagus had poor sleep quality and was a higher risk of OSA.[27] Chen et al. found that the incidence of high-risk OSA in the GERD group was significantly higher than that in the non-GERD group. Further, the incidence of high-risk OSA in patients with reflux esophagitis was significantly higher than that in patients with non-erosive reflux disease and the control group. At present, the main mechanisms of GERD aggravating OSA are as follows: (1) Gastric contents regurgitated to esophagus stimulate respiratory chemoreceptors, causing bronchoconstriction, vagal hyperreflexia, aggravating upper respiratory tract obstruction, and hypoventilation; (2) Night reflux causes awakening and sleep fragmentation, which may aggravate daytime sleepiness of OSA patients.[28] (3) Gastroesophageal reflux can cause congestion and edema of oropharyngeal tissue, causing reflux pharyngolaryngitis and aggravate upper respiratory tract obstruction. Gastroesophageal reflux can cause congestion and edema of oropharyngeal tissue, causing reflux pharyngolaryngitis and aggravating upper respiratory tract obstruction.[29] However, our study did not explore the prevalence of OSA in patients with GERD, which may be a direction for future studies.
This study found that the incidence of chronic diseases, such as hyperlipidemia, diabetes, and coronary heart disease, was significantly higher in the GERD group than in the non-GERD group. A possible reason is that middle-aged and elderly populations have a high prevalence of chronic diseases such as diabetes, coronary heart disease (CHD), and hyperlipidemia. OSAHS and GERD are also risk factors for chronic diseases, such as hyperlipidemia, diabetes, CHD, and hypertension. A meta-analysis showed that metabolic syndrome is a risk factor for GERD, and among the abnormal metabolic components that establish the diagnosis of metabolic syndrome, abdominal obesity, hypertriglyceridemia, hyperglycemia, and hypertension are risk factors.[30] In addition, a large number of previous studies have shown that diabetes mellitus is a risk factor for GERD.[31] A cohort study also showed that GERD is closely associated with CHD. Patients with GERD had a greater probability of CHD than those without GERD (log-rank test, P < 0.001 and 11.8 vs 6.5 per 1000 person-years). The GERD cohort had a higher risk of CHD than the comparison cohort after adjusting for multiple risk factors (adjusted hazard ratio, 1.49; 95% confidence interval [CI]:1.34–1.66).[32] Our results are generally the same as those of previous studies, and showed that middle-aged and elderly patients with OSAHS complicated by GERD were more likely to have diabetes, hypertension, CHD, and other chronic metabolic diseases. When GERD is complicated by these metabolic diseases, it will have a greater impact on the quality of life, treatment, and survival prognosis of patients and will impose a more severe economic burden on patients, making treatment more difficult.
Regarding the treatment of patients with OSA and GERD, previous studies have shown that CPAP treatment can improve the symptoms of GERD or even result in recovery in patients with OSAHS and GERD.[33, 34] A 2020 review summarized two reflux symptom scores and four pH parameter indexes and showed that CPAP treatment in patients with OSAHS complicated with GERD could improve reflux symptoms and reduce pH. CPAP therapy is considered an important means of improving OSA and reflux.[35] Our follow-up results suggested that two months of CPAP treatment can significantly improve the positive symptoms of GERD and may even lead to recovery. This effect might be related to the increase in intrathoracic pressure and the decrease in the pressure difference between the upper and lower diaphragms from CPAP treatment, while reducing the time for lower esophageal sphincter relaxation during a brief awakening.[36] CPAP treatment improves OSA, and upper respiratory tract obstruction and decreases intra-abdominal pressure, thus reducing reflux. In addition, studies have shown that long-term use of PPI may lead to kidney injury, enteric infections, and other adverse reactions.[37, 38] We found that the CPAP + PPI treatment group had a higher PPI withdrawal rate after eight weeks than the PPI treatment group. Thus, our study provides a novel finding that CPAP + PPI treatment is effective in reducing the adverse events caused by PPI use in GERD patients complicated with OSA.
Almost all previous studies on the treatment of OSA complicated with GERD and CPAP have focused on the improvement of gastrointestinal symptoms. Only a small number of studies explore the therapeutic effect of PPI in OSA complicated with GERD. Studies have shown that in OSA complicated with GERD treated with PPI, AHI, apnea, and hypopnea conditions can be significantly improved after PPI treatment.[39, 40] In addition, anti-reflux therapy may improve daytime somnolence in patients with GERD and OSA.[41] Studies have shown that PPI combined with CPAP treatment can improve OSA and GERD better than CPAP treatment alone; however, related studies are rare. It may be our next research direction.
From this retrospective and follow-up study, we can arrive the conclusions that the prevalence of GERD is high, which is associated with age and the severity of OSA. OSA patients with GERD are more likely to suffer from chronic diseases such as diabetes, coronary heart disease, and hyperlipidemia. In OSA patients with GERD, CPAP treatment can improve the symptoms of reflux heartburn and reduce the use of PPI. Patients who suspected OSA should be actively concerned about their GER symptoms. Patients with OSA complicated with GERD should be actively given CPAP treatment.
Our study has some limitations. Our patients are outpatients or inpatients in Beijing, China, and cannot represent all OSA patients, and they were diagnosed OSA by HSAT, which may lead to misclassification of the OSA diagnosis and OSA severity.[18] In addition, this is a retrospective study, our sample size ass small, and did not obtain objective findings for GERD. Finally, we followed up a small simple of patients with OSA complicated with GERD. Large, multicenter, prospective studies are needed to support our conclusions.