Study subjects
This study recruited 42 “globus pharyngeus” patients (G group) and 38 non-globus pharyngeus patients (NG group) depending on whether they had abnormal laryngopharyngeal sensations. For “globus pharyngeus”, the Rome III definition was met except with the exception of that for reflux disease which was not objectively assessed. All cases were performed using High Resolution Manometry in Gastrointestinal Motility Suit, First Affiliated Hospital of Dalian Medical University from December 1, 2015 to May 1, 2016. The two groups were further divided into laryngopharyngeal non-reflux groups (G-NR group, NG-NR group) and laryngopharyngeal reflux groups (G-R group, NG-R group) according to the laryngopharyngeal Reflux Symptom Index (RSI) and the response to PPIs treatments [7]. This study was approved by the hospital ethics committee (No. LCKY2016–33), and all participants in the study signed the informed consent form.
Inclusion and exclusion criteria
Inclusion and exclusion criteria of the G-NR group (N = 20)
Inclusion criteria
a. Conformed to Rome III criteria for globus [8]: 1) persistent or intermittent, non-painful sensation of a lump or foreign body in the throat; 2) occurrence of the sensation between meals; 3) absence of dysphagia or odynophagia; 4) absence of evidence that gastroesophageal reflux is the cause of the symptom (see b. d. e.); 5) absence of histopathology-based esophageal motility disorders. Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis. b. no positive sign of inflammation, or only slight inflammation found through the electronic laryngoscopy and electronic gastroscopy; c. no history of drug use within the last 1 month; d. no response to double-dose of PPIs treatment for 8 ~ 12 weeks: no improvement in laryngopharyngeal symptoms; e. RSI scores < 13 [7].
Exclusion criteria
a. Accompanied by malignant tumor, immune system disease, metabolic disease, heart and lung diseases and severe local infection, etc.; b. unable to tolerate the esophageal pressure test performed by High Resolution Manometry.
Inclusion and exclusion criteria of the G-R group (N = 22)
Inclusion criteria
a. Abnormal feelings such as persistent or intermittent foreign body, formication sign, burning, tightening, muffled, narrow sense and sputum adhesion were exhibited in the oropharynx and suprasternal fossa, without the presence of dysphagia, sore throat or difficulty swallowing and/or breathing; b. no positive sign of inflammation, or only slight inflammation found through the electronic laryngoscopy and electronic gastroscopy; c. no history of drug use within the last 1 month. d. response to PPIs treatment. e. RSI scores ≥ 13 [7].
Exclusion criteria
Others are in agreement with those of the G-NR Group.
Inclusion and exclusion criteria of NG-NR group (N = 20)
Inclusion criteria
No symptoms of globus pharyngeus, such as laryngopharyngeal dryness, tightness, burning, obstruction or foreign body sensation; no sore throat, difficulty swallowing and/or breathing; but received the high resolution esophageal motility test for non-cardiac chest pain, i.e., pain or discomfort behind the sternum without any cardiopulmonary diseases. Other inclusion and exclusion criteria are in agreement with those of the G-NR Group.
Inclusion and exclusion criteria of NG-R group (N = 18)
Inclusion criteria
No symptoms of globus pharyngeus, but received esophageal pressure measurements because of the mild discomfort behind the sternum. Other inclusion and exclusion criteria are in agreement with those of the G-R Group.
Questionnaires
The study participants completed the questionnaires under the guidance of a member of the study team who was present to ensure that the participants understood the forms clearly. However, the study member was prohibited from using any suggestive words regarding any of the questions.
General information
The general questionnaire included information about name, demographic data (age and gender), marriage, occupation, education, income, concomitant diseases, medications in use and family history.
RSI version
Patient information related to LPR symptoms was gathered through a questionnaire containing the validated version of RSI. The RSI score was applied as proposed by Belafsky et al., and LPR diagnosis was based on the RSI score ≥ 13 [7, 9]. A self-administered nine-item RSI was completed by the patients in less than 1 min. The score for each item ranged from 0 (none) to 5 (most severe) with a maximum total score of 45. The nine items included:1) hoarseness or a problem with your voice; 2) clearing your throat; 3) excessive throat mucus or postnasal drip; 4) difficulty swallowing food, liquids or pills; 5) coughing after eating or lying down; 6) breathing difficulties or choking episodes; 7) troublesome or annoying cough; 8) sensation of something sticking in your throat or a lump in your throat; 9) heartburn, chest pain, indigestion, or stomach acid reflux (Additional file 1).
Life exposure factors questionnaire [9,10,11]
Life exposure factors concerning behavioral characteristics probably related to globus pharyngeus were gathered through a questionnaire containing 17 items: smoking, alcohol, tea, coffee, chocolate, spicy food, greasy meal, fullness, high salt, night work, staying up late, fatigue, pressure, constipation, loneliness, anxiety and depression (Additional file 2).
Esophageal motility measurement
High resolution manometry was performed using a 24-channel water-perfused catheter of 4.0 mm in diameter as used previous studies [12](Ningbo Maida Medical Device Inc., Ningbo, China). Side hole 1, which starts at the most distal point, was 5 cm from hole 2. Holes 2–7 were 1.0 cm from each other and holes 8–24 were 1.5 cm from each other. Once placed, it covered the entire length of the esophagus from the upper esophageal sphincter to the lower esophageal sphincter with an additional channel in the stomach. The data acquisition frequency was 20 Hz for each sensor. Computer analysis software (Video was recorded by MedSample360 at a rate of 20 frames/s and analyzed by MedView360) was used to assess various esophageal motility parameters.
The patients were asked to fast for 12 h for foods and 6 hours for water before the measurement. The high resolution esophageal motility test was performed in a supine position. Firstly, a 30-s period of basal recording was obtained after the appropriate placement of the catheter. Then, the patient was asked to swallow 5 ml of water and the swallow was repeated for a total of 10 times with a 30-s interval between consecutive swallows. Lastly, multiple rapid swallows (5 swallows of 2 ml of water with 2- to 3-s intervals) were performed. The resting pressure and residual pressure of the UES and low esophageal sphincter (LES), as well as the esophageal distal contractile integral (DCI), were recorded.
Statistical analysis
All data were inputted into the SPSS 22.0 software package for processing. The λ [2] test was used for analysis of the correlation between the G group, the NG group and life exposure factors. The categorical data was shown using the percentage and analyzed by the λ [2] test. The measurement data are presented as mean ± standard deviation (x ± s). The Student’s t test was used for comparison between two groups. The significance level for all hypothesis testing (p-value) was 0.05.