Background
Globus pharyngeus is one of the most common diseases encountered in otolaryngology clinics. However, the treatment of globus pharyngeus still has some major problems with low cure rate and high recurrence. Similar patients may often be seen by gastroenterologists [
1‐
3]. Manifestations of globus pharyngeus include, but are not limited to, laryngopharyngeal dryness, tightness, burning, obstruction, and foreign body sensation. However, these symptoms are not accompanied by sore throat or difficulty swallowing and/or breathing. The etiologies of globus pharyngeus are very complicated, including the diseases of the pharynx and its adjacent and/or distant organs, systemic disorders, mental factors and functional diseases. With the development of clinical technologies, a large number of studies have been performed [
2,
3]. In these studies, researchers found a close relationship between globus pharyngeus and backflow of gastric contents into the throat. In 1987, Wiener et al. placed probes into the esophagus and on the top of the upper esophageal sphincter (UES) to detect pH over a course of 24 h using double-probe pH testing. They found that patients with globus pharyngeus had laryngopharyngeal acid reflux. In 1989, they once again used the similar methods to monitor pH over 24 h in 32 patients with globus pharyngeus. However, this time they reported that the symptoms and the acid reflux times of these patients were all different from gastroesophageal reflux disease (GERD), and esophagitis was hardly found. Since then, research on globus pharyngeus has been extensively performed [
4]. Although the results were not completely consistent, laryngopharyngeal reflux (LPR) was officially adopted by the American Academy of Otolaryngology-Head and Neck Surgery in 2002 [
5]. However, whether there was a close relationship between globus pharyngeus and laryngopharyngeal reflux and/or gastroesophageal reflux still left some doctors feeling confused. One study showed that abnormal laryngopharyngeal or esophageal reflux was not indicated by pH-impedance monitoring in some patients with suspected LPR refractory to proton pump inhibitors (PPIs) treatments. The results proved that LPR is unlikely in these patients [
6]. It can be induced that globus pharyngeus patients with non-LPR (G-NR) also account for a certain proportion. At present, there is no report about the etiologies and influence factors of these patients. This study was performed to clarify the related factors of the symptoms of globus pharyngeus refractory to PPIs treatments and to learn more about G-NR so as to improve the curative effect.
Discussion
In this study we have found that the average resting and residual pressures of the UES in the patients with globus pharyngeus without laryngopharyngeal reflux were higher than in the patients without globus pharyngeus. The patients with globus pharyngeus but no laryngopharyngeal reflux showed higher incidences of stress, smoking, alcohol-drinking, high-salt and anxiety than the patients without globus pharyngeus or laryngopharyngeal reflux.
The symptoms of globus pharyngeus are usually present with dry swallowing rather than swallowing food [
13]. They may be intermittent or sustainable, often accompanied by other symptoms such as belching or chest tightness [
14,
15]. The etiologies and mechanisms of globus pharyngeus have been unclear [
16]. Some studies suggested that these symptoms might be associated with rhinitis, sinusitis, thyroid diseases, sore throat, GERD, gastroduodenal ulcer, iron deficiency anemia, psychological disorders, etc. [
17,
18]. However, most researchers consider globus pharyngeus as a series of symptoms without organic diseases that are more like hysteria defined as a subjective feeling of throat discomfort.
Wada [
19] reported that GERD could cause globus pharyngeus. LPR is believed to be attributed to abnormal motility of the UES and may often arise in daytime or in an upright position, especially during a physical exertion. If the PPI treatment is effective, the diagnosis of LPR can be considered. Otherwise further examinations are needed to determine the etiologies of globus pharyngeus [
20‐
22].
The HRM system can provide clear, intuitive and accessible images and data of esophageal motility. However, there have been limited reports on the assessment of globus pharyngeus using the HRM techniques [
23]. Our results showed that the resting and residual pressures of the UES in the globus pharyngeus group were higher than those of the non-globus pharyngeus group. These elevated UES pressure may be responsible to cause symptoms of globus via the vagal afferent pathway. The UES plays an important role in preventing reflux of esophageal contents through the throat and into the mouth. It was also found in this study that the resting and residual pressures of the UES in patients with globus and LPR were higher than those in patients with globus but no LPR; this elevation might be attributed to stimulation of the UES by the refluxed gastric acid [
24].
The results of our study showed that patients with LPR with or without globus showed a reduced LES pressures in both resting and residual states, suggesting that symptoms of LPR might be caused by a low pressure of LES which is known to be a decisive factor in the occurrence of gastroesophageal reflux. Furthermore, the refluxed gastric acid could stimulate the ring pharyngeal muscle around the UES and result in spasms [
24,
25]. The fact that patients with globus but no LPR exhibited normal LES pressure suggested that globus pharyngeus might not be associated with gastroesophageal reflux.
In this study, no significant difference was noted in DCI between the G-NR and NG-NR groups, indicating normal esophageal body motility in G-NR patients. However, the DCI in the G-R and NG-R groups was reduced in comparison with the NG-NR group, suggesting that abnormal esophageal body motility could occur in both reflux groups with and without globus pharyngeus. Most of previous studies were performed in the G-R group and yielded similar results [
1,
26], whereas, little attention has been pain in the G-NR group. Weak distal esophageal smooth muscle contractions result in feeble peristalsis and decreases scavenging abilities of bolus and refluxed stomach contents. The residual food and refluxed acid may then stimulate the local esophagus, aggravating symptoms of laryngopharyngeal abnormal sensation [
27,
28]. On contrary, the globus symptoms in the G-NR patients who showed normal DCI or peristalsis could not attributed to acid reflux or food/bolus retention. Taken together, the symptoms in the G-NR patients might be attributed mainly to the high pressure of the UES.
The life exposure factors play an important role in the occurrence and development and even treatment of diseases [
11]. This study further explored relationships between age, sex, and life exposures in the G-NR. The mean age and median age of the patients in each group were all within the World Health Organization-specified middle-age range. Accordingly, the middle age could be regarded as a risk factor for globus pharyngeus, as in the cases of G-NR groups. Compared with the NG group, the G group had a higher incidence of smoking, alcohol consumption, eating high salt, and anxiety as well as a higher prevalence of globus pharyngeus in female. The incidence of globus pharyngeus was previously reported to be correlated with both anxiety and depression [
29,
30]; however, the depression as a risk factor was not indicated in this study. Furthermore, we compared the G-NR group with the G-R group and found that the incidence of smoking, drinking and anxiety was lower in the G-NR patients. Combined with the above mentioned factors, the incidence of globus pharyngeus without reflux may be more likely to occur in middle-aged women, especially those with smoking habits, high rates of alcohol consumption and anxiety, but these habits have been shown to be more common in patients with reflux symptoms. Further, we compared the G-NR group with the NG-NR group and found a higher incidence of smoking, alcohol consumption, high salt consumption, stress and anxiety in the G-NR patients; in addition, the prevalence of globus pharyngeus was higher in female than male.
This study was limited in a number of issues:
a) The number of patients recruited was limited, so a multi-center and large sample study could be performed.
b) In our study, the NG-NR group acted as the control group only according to the RSI scores and responses to proton pump inhibitors (PPIs) treatments which may be used as objective parameters with low cost and high practicality [
31,
32]. 24-h pH monitoring was not performed during the experiment to completely exclude the possibility of reflux [
33].