Scintigraphic Evaluation of Esophageal Motility and Gastroesophageal Reflux in Patients Presenting with Upper Respiratory Tract Symptoms

Introduction

Gastroesophageal reflux disease (GERD) is very common among the population in present day's stressful life due to various reasons. Chest burn or burning chest, the most common symptom of gastroesophageal reflux, is the major reason for consumption of antacids in our society. GERD can be overlooked for several reasons: first, the most common symptoms, chest burn and regurgitation, occur in only half of these patients; second, because of the natural history of the disease and the frequency of its spontaneous remission, many patients do not seek medical advice; and third, there is no diagnostic standard for GERD.

Symptoms of GERD are divided into two categories: esophageal, which includes typical esophageal reflux complaints (chestburn, regurgitation of food, and dysphagia) and noncardiac chest pain, and extraesophageal, which includes pulmonary (asthma and recurrent aspiration pneumonia), otolaryngologic (morning hoarseness, halitosis, excessive phlegm, frequent throat clearing, dry mouth, coated tongue, sensation of a lump/foreign body in the throat, throat tickle, chronic sore throat, nocturnal cough, chronic or recurrent cough, and difficulty in breathing (especially at night), closing off of the airway (“laryngospasm”), and dyspeptic symptoms (upper abdominal pain, nausea, vomiting, and bloating).

The typical esophageal symptoms occur only in 50%–65% with this disorder.[1] Respiratory/extraesophageal manifestations are less recognized but appear to occur frequently as a complication of reflux. Posterior laryngitis appears particularly relevant, occurring in 50%–60% of patients with GER[1] who present clinically with otolaryngeal symptoms.

The evaluation of these patients should include confirmed evidence of pathologically significant GER, excluding motility disorders involving esophagus and stomach, ruling out structural lesions of esophagus and stomach particularly involving lower esophageal sphincter/gastroesophageal junction, and finally, grading the severity of reflux.

A number of methods have been used to assess esophageal transit (ET) and GER. Scintigraphy is a noninvasive method in which the test meals and acquisition procedures have been standardized, and the results are largely operator independent. The principal disadvantages of scintigraphy are the need for exposure to ionizing radiation and the costs associated with the procedure. However, the radiation burden to the patient in this scintigraphic procedure is much less when compared to the fluoroscopic barium swallow.

In this context of evaluation of patients presenting with otolaryngeal symptoms, certain questions remained unanswered. Does ET scintigraphy (ETS) play a role in addition to gastroesophageal scintigraphy in influencing the treatment of these patients? Does a positive scintigraphic finding in a symptomatic patient with normal nasopharyngolaryngoscopy (NPL) have any significance? Is there a correlation between GER, NPL, and esophageal motility?

Hence, this study was performed to provide answers to the aforementioned questions with the primary aim to assess the utility of gastroesophageal scintigraphy (GES) in adult patients presenting with otolaryngeal symptoms suspected to be due to acidic and nonacidic GER disease. Secondary aim was to assess ET in patients with recurrent otolaryngeal symptoms and to assess the importance of correlation between GER, NPL, and esophageal motility.

Materials and Methods

This prospective study was performed in the Nuclear Medicine Department, Apollo Hospitals at Chennai, during a period of 1 year from May 2015 to May 2016. A total of 30 patients (18 males, 12 females; age range - 19–60 years; mean age +

standard deviation [SD] - 37.9 + 10.2 years) who had undergone flexible fiber-optic transnasal NPL were included in the study. All these patients underwent GES which included the ET study in erect and supine position as well.

Ten healthy volunteers served as a control group (6 males, 4 females; age range - 19–74 years; mean age +

SD - 34.7 + 8.0 years). None had a history of gastroesophageal disease, central nervous system disease, peripheral neuropathy, diabetes mellitus, or other systemic diseases commonly associated with gastroesophageal dysfunction. In addition, none had a recent history of drug treatment potentially affecting gastroesophageal function. Informed consent was obtained from all study participants, and the study was approved by ethical committee of the Apollo Hospitals. The images were interpreted by two experienced nuclear medicine physicians.

Interpretation

Esophageal transit study

Delayed transit if <90% of bolus is cleared in 7 s in erect position [Figure 5 and 6] and in 10 s in supine position [Figure 7 and 8].[2] ET is determined based on the amount of residual activity in the esophagus using the formula C(t) = Emax–E(t)/Emax, where C(t) represents the percentage of esophageal emptying at time t, Emax, the maximal count rate in the esophagus, and E(t), the esophageal count rate at time t.

Close

Figure 1 No reflux – Normal scan

Export to PPT

Close

Figure 2 Grade I GER – Visualization of tracer in distal 1/3^rd of esophagus

Export to PPT

Close

Figure 3 Grade II GER – Visualization of tracer in middle 1/3^rd of esophagus

Export to PPT

Close

Figure 4 Grade III GER – Visualization of tracer in proximal 1/3^rd of esophagus

Export to PPT

Close

Figure 5 Normal esophageal transit in erect position

Export to PPT

Close

Figure 6 Delayed esophageal transit in erect position

Export to PPT

Close

Figure 7 Normal esophageal transit in supine position

Export to PPT

Close

Figure 8 Delayed esophageal transit in supine position

Export to PPT

Gastroesophageal reflux

Presence of spikes of tracer activity (>4% of gastric activity[3]) in the esophagus in any of the frames is considered as a gastroesophageal reflux. Absence of any spike of tracer activity in all the frames is considered as a normal scan with no reflux [Figure 1]. Reflux was quantified using regions of interest over the esophagus and stomach using the formula R = E(t)–E(b) × 100/Go, where R is the percentage of reflux material into the esophagus; E(t), the esophageal counts at time t; E(b), the paraesophageal background counts; and Go, the gastric counts at the beginning of the study.

Discussion

Chronic cough is a common and distressing symptom.[5] The association between cough and GER is now well recognized.[678] Indeed, GER is one of the most frequent causes of chronic cough, accounting for 10%–40% of cases. The pathophysiologic mechanisms underlying GER-related cough are not fully understood but may include microaspiration of esophageal contents into the larynx and tracheobronchial tree or a vagally mediated esophageal-tracheobronchial reflex.[910] A self-perpetuating cough-reflux cycle has been proposed in which esophageal acid stimulates cough, and cough, in turn, amplifies reflux by increasing transdiaphragmatic pressure.[1011] The primary event in GER is the movement of gastric contents into the esophagus. There are several possible mechanisms whereby impaired ET could contribute to GER-related cough. A delay in ET could increase the rate of transient lower esophageal sphincter relaxations.[12] Second, impaired esophageal clearance may lead to slow clearance of esophageal acid, which has been implicated in the pathogenesis of some cases of chronic cough.[913]

In our study, we found significant correlation between the GER and the findings documented by NPL in 28 out of 30 patients (P < 0.001). The more the grade of reflux, the more severe was the NPL findings documented in terms of posterior laryngitis, congested arytenoids, cobblestone appearance in posterior pharyngeal wall, etc. These findings underscore the fact that direct contact with gastric contents as the major cause of reflux-associated posterior laryngitis. Two patients in whom scintigraphy demonstrated Grade II reflux had a normal NPL suggesting that structural inflammatory changes due to acidic pH of refluxate have not yet manifested or the symptoms could be due to nonacid refluxate [Tables 3, 5, and 10].

Table 1 Scintigraphic grading of gastroesophageal reflux in controls with corresponding nasopharyngolaryngoscopy findings

Table 2 Incidence of delayed esophageal transit in various grades of gastroesophageal reflux in controls

Table 3 Scintigraphic grading of gastroesophageal reflux in cases with corresponding nasopharyngolaryngoscopy findings

Table 4 Incidence of delayed esophageal transit in various grades of gastroesophageal reflux in cases

Table 5 Incidence of abnormal esophageal transit in symptomatic patients with corresponding nasopharyngolaryngoscopy report

Table 6 Percentage of refluxate in patients with various grades of gastroesophageal reflux

Table 7 Incidence of gastroesophageal reflux in cases and control

Table 8 Comparison of esophageal transit in erect position. cases and control

Table 9 Comparison of esophageal transit in supine position. cases and control

Table 10 Scintigraphic grade of gastroesophageal reflux and nasopharyngolaryngoscopy cross-tabulation

Substantiating our findings, Songür et al.[14] and Bestetti et al.[15] have observed similar findings in their respective studies that showed that severe grade of esophagitis and the posterior laryngitis were more common, and frequency of reflux episodes, their duration, and percentage volume of gastric contents were significantly higher in the patients with proximal reflux (reflux reaching the upper third of esophagus, i.e., Grade III) than in patients with distal reflux (reflux into the lower third of esophagus, i.e., Grade I) [Tables 1, 2, 6 and 7].

In our study, when we evaluated the incidence of esophageal motility disorder in the patients and assessed the relationship between GER and esophageal transit, 67% (2/3) of patients with no scintigraphic evidence of GER showed delayed ET in supine position. Nearly 80% (4/5) of patients who had Grade I GER showed delayed ET in supine position. From those patients who had Grade II GER, 60% (3/5) had delayed ET in supine position while 20% (1/5) showed delay in the erect position as well. Finally, of those patients categorized as having Grade III GER, 64% (11/17) showed delayed transit while erect and 100% (17/17) displayed delayed ET in supine position. The incidence of esophageal motility disorder was statistically significant in our cases compared with controls (P < 0.019 for erect position, P < 0.001 for supine position) [Tables 8 and 9]. Hence, GERD patients not only have a higher incidence of esophageal motility disorder than the normal population, but patients with esophageal motility disorder also had significantly more GER and delayed clearance, particularly those presenting with extraesophageal symptoms (cough, asthma, and laryngitis). Similar results were postulated by Fouad et al.[16] and Ho et al.[17] in respective studies that esophageal motility disorder is seen in 50% of patients with extraesophageal symptoms compared to only 19% of patients with heartburn.

From our study, in patients who had symptoms but showed no demonstrable GER, more than half showed delayed ET in supine position. This finding indicates that esophageal dysmotility may manifest earlier than GERD becomes demonstrable. Hence, abnormal esophageal motility can be the primary disorder leading to delayed esophageal acid clearance, in turn, causing increased exposure of the esophageal, pharyngeal, and laryngeal mucosa to the acidic and other irritant contents of the gastric refluxate causing otolaryngeal symptoms, substantiated by the concept put forth by Songür et al.[14] and Bestetti et al.[15] Overall, our study shows strong evidence for the causal relationship of ineffective esophageal motility and otolaryngeal symptoms [Tables 4 and 5].

Whether esophageal motility disorder is a primary motility disorder causing GER disease and otolaryngeal symptoms or is merely an effect related to acid-induced injury to the esophagus is still controversial. Some studies suggest that gross pathologic injury to the esophagus is an important part of the pathophysiology of motility change, and improvement in esophageal clearance can be achieved by the healing of esophagitis.[1819] However, other studies show no differences of ET time and motor response to reflux between patients with esophagitis and controls.[2021]

In our study, when we assessed the correlation between GER, NPL findings, and esophageal motility, we found an interesting observation supporting the concept put forward by Eriksen et al.[20] and Timmer et al.[21] Out of three symptomatic patients with no demonstrable GER but with abnormal esophagealtransit, there were no abnormal findings in nasopharyngolaryngoscopic examination. The nasopharyngolaryngoscopic findings were significant as the grade of GER becomes higher similar to those observed by Songür et al.[14] and Bestetti et al.[15] Our study showed that there was no correlation found between the nasopharyngolaryngoscopic findings and esophageal transit. Similarly, Ho et al.[17] found no correlation between esophagitis on endoscopy and esophageal motility. Lemme et al.[22] in their study concluded that there were no differences between the severity of ineffective esophageal motility in erosive and in nonerosive GERD patients. However, there was a linear statistically significant association between the grade of GER and the NPL findings [Table 10] (P < 0.001).

Similar findings were observed in the study by Ho et al.[17] in which they found that 56.7% of patients without endoscopic esophagitis had IEM. They showed that GERD patients with IEM did not have more endoscopic esophagitis than patients with normal manometry. No correlation was found between the endoscopic esophagitis and esophageal motility like our study. The only contrary was that our study had NPL as documentation for mucosal injury instead of upper GI endoscopy in the other studies. These results would indicate that IEM is an integral part of GER disease and is more of a cause than an effect[2023] and may not always be associated with mucosal injury.

Conclusion

Gastroesophageal scintigraphy was able to demonstrate significant GER in patients presenting with otolaryngeal symptoms without the typical GI symptoms. ETS could effectively document the presence of esophageal motility disorder in a simple, noninvasive manner entailing a low radiation burden and closely reflecting the normal physiology. ETS objectively showed the coexistence of esophageal motility disorder in most of the patients presenting with otolaryngeal symptoms even without an associated reflux disease. We suggest esophageal transit/gastroesophageal scintigraphy should be included in the routine workup of all the patients with recurrent otolaryngeal symptoms and may be useful for monitoring response to therapy. Our study suggests possibility of ineffective esophageal motility being the primary disorder leading to otolaryngeal symptoms in most of the patients along with associated reflux disease. This needs to be evaluated in larger patient cohort.