Gastroesophageal Reflux Symptoms in Typical and Atypical GERD

Roles of Gastroesophageal Acid Refluxes and Esophageal Motility

Tanisa Patcharatrakul; Sutep Gonlachanvit


J Gastroenterol Hepatol. 2014;29(2):284-290. 

In This Article


The typical GERD symptoms including heartburn and acid regurgitation have been shown to be associated with abnormal esophageal acid exposure.[1] Although little information on the association of gastroesophageal acid refluxes and laryngo-pharyngeal symptoms is available, the reflux symptom index (RSI) which includes typical reflux, respiratory and pharyngeal symptoms has been used for the diagnosis of laryngopharyngeal reflux disease.[21]

The interplay between esophageal motility disorders and gastroesophageal refluxes on the development of GERD symptoms has not been clearly known. It has been reported that ineffective esophageal motility disorder associated with prolonged esophageal volume clearance and retrograde bolus escape,[22,23] theoretically, may produce more regurgitation, cough, and other ENT or respiratory symptoms. In addition, ineffective esophageal dysmotility itself can produce heartburn or chest pain irrespective of gastroesophageal acid refluxes in previous studies[24–27] possibly due to sustained longitudinal esophageal contractions and reduced esophageal wall blood flow. Therefore, evaluation of the association between gastroesophageal acid refluxes and these symptoms should be evaluated together with esophageal motor functions.

In our study, we found that acid regurgitation symptom was associated with abnormal gastroesophageal acid refluxes with no significant effect of esophageal dysmotility on the symptom. This may suggest that there is usually no esophageal contraction during the occurrence of regurgitation. Patients with abnormality of either esophageal manometry or pH study had similar prevalence of dysphagia and hoarseness of voice symptoms compared to patients with normal results of both tests, whereas prevalence of dysphagia, chronic cough and hoarseness of voice symptoms were increased in patients with both abnormal gastroesophageal acid refluxes and abnormal esophageal motility test results. This suggested that gastroesophageal acid reflux may enhance the expression of dysphagia in patients with esophageal dysmotility, and esophageal dysmotility may contribute to the development of hoarseness of voice and cough symptom in patients with positive pH tests. We observed that most patients with chronic cough who were refractory to PPI but had low amplitude segmental simultaneous esophageal contraction or diffuse spasm responded well to smooth muscle relaxant (nitrate) (data were not shown). This finding not only demonstrate the interplay of esophageal motility and esophageal acid exposure but also encourage further evaluations by esophageal manometry and pH testings in the patients with extraesophageal symptoms especially who have chronic cough or hoarseness of voice symptoms refractory to acid suppression. Due to the fact that our hospital is a referral center, esophageal dysmotility and extraesophageal symptoms were presented in quite high prevalence. Among the 93 patients who had abnormal esophageal manometry results in our study, 88.2% were diagnosed as ineffective esophageal motility. Eight patients had nutcracker esophagus, and three patients had diffuse esophageal spasm. All of these 11 patients had symptoms suggestive of GERD that fulfilled our inclusion criteria (typical reflux, eight; noncardiac chest pain, two; chronic ENT symptom, one), and four of these patients also had positive either upper or lower pH test. This supported previous findings that ineffective esophageal motility is the most common esophageal dysmotility in GERD, and other esophageal dysmotility including nutcracker esophagus and diffuse esophageal spasm can also be found,[6,10,28] and we therefore included all patients with these esophageal dysmotilities for analysis. However, after only the patients with ineffective esophageal motility were analyzed, the outcomes did not change from described above. This suggests that the association between esophageal dysmotility and dysphagia or ENT symptoms in our study was the effect of ineffective esophageal contractions. A previous study in Korean patients by Lee et al. suggested that there was no significant effect of ineffective esophageal motility on typical GERD and laryngopharyngeal symptoms.[29] They found that only heartburn symptoms were associated with concurrently abnormal esophageal acid exposure and ineffective esophageal motility. However, the sample size of patients with ineffective esophageal motility in their study was too small (n = 32), which may lead to type II error of their conclusions.

The acid regurgitation symptom was associated with both significant upper and lower esophageal acid exposure. The higher prevalence of acid regurgitation symptom compare to the prevalence of heartburn symptom in our patients suggests that certain episodes of gastroesophageal acid reflux are not perceived as burning sensation by the esophagus which is different from the data of western countries. Heartburn and acid regurgitation were developed by different pathophysiologic mechanisms. Heartburn has been reported to be induced by chemical stimulation such as acid or capsaicin in the esophagus and sustained contractions or thickening of the esophageal wall,[24–27] but acid regurgitation developed when the regurgitated gastric content moves up to the throat or oral cavity. We hypothesized that capsaicin in chili may mask heartburn symptom because Thais generally consumed spicy foods, and capsaicin mediate painful and burning sensation in gastrointestinal tract via TRPV1 receptors. A preliminary study in our laboratory also suggested that chronic ingestion of chili can decrease heartburn symptoms.[30,31] We do not think Thai patients misunderstand the meaning of "heartburn" because we also found that acid perfusion tests (data were not reported in this study) did not induce any symptoms in most of the patients in our study which correlated with the low prevalence of heartburn. The term "heartburn" and "acid regurgitation" in Thai language are easy to describe by the patients, and our finding was not due to the language issue. These may explain why there was no correlation of heartburn symptoms and pH test results in our patients. Moreover, we found that prevalence of heartburn symptoms in the patients with either abnormal results of esophageal manometry or pH test were similar but significantly higher than in patients with normal of both esophageal manometry and pH test. This finding supports the previous reports on the mechanism of heartburn symptom other than esophageal acid exposure, which probably is the role of esophageal dysmotility.[24–27]

Ineffective esophageal contractions can be associated with cough symptoms by contribution to higher refluxes of gastric contents leading to more prevalence of micro-aspiration and cough. In addition, esophageal dysmotility has been reported to be associated with bronchial hyperresponsiveness to methacholine.[32] Thus, patients with esophageal dysmotility may also have airway hyperresponsiveness to micro-aspiration of reflux contents and explains the results of our study.

Old age, obesity, and male patients were previously reported to be associated with more reflux symptoms and esophagitis.[33–36] Although we found that older age was significantly associated with more prevalence of positive lower esophageal pH test, subgroup analysis showed that this association was demonstrated only in patients with abnormal esophageal manometry but not in patients with normal manometry. Thus, the association between older age and higher prevalence of significant lower esophageal acid exposure possibly depends on the presence of esophageal dysmotility. Aging is associated with many esophageal physiologic changes that could exacerbate refluxes. Previous studies reported the age-related impairment of esophageal motility including low amplitude esophageal contraction as well as ineffective esophageal peristalsis, which were associated with prolonged esophageal acid clearance.[37,38] BMI was not significantly associated with esophageal pH and esophageal motility test results in our study. This finding could result from most of our patients having relatively normal BMI (less than 25 kg/m2).

Since most GERD patients in our study had non-erosive GERD, the results in our study should not be applied to erosive reflux disease. Further investigations are needed to demonstrate the interplay between abnormal gastroesophageal acid reflux and esophageal dysmotility on typical and atypical GERD symptoms in erosive reflux disease patients.

In conclusion, acid regurgitation, dysphagia, hoarseness of voice, and chronic cough were associated with gastroesophageal acid refluxes in our patients with typical and atypical gastroesophgeal reflux symptoms. Acid regurgitation symptom but not heartburn was associated with gastroesophageal acid reflux in our patients. Esophageal dysmotility had no significant effect on the development of acid regurgitation symptom, whereas chronic cough, hoarseness of voice, and dysphagia symptom were associated with esophageal dysmotility only in patients with abnormal esophageal acid exposure. This study demonstrated the interplay between ineffective esophageal motility and gastroesophageal acid refluxes on the pathogenesis of typical and atypical GERD symptoms.