Comparison of oesophageal function tests between Chinese non-erosive reflux disease and reflux hypersensitivity patients

The study received ethics approval from the local ethics board of Beijing Anzhen Hospital, Capital Medical University. All participants gave written informed consent.

Chinese patients who presented with a main symptom of heartburn with a normal upper gastrointestinal endoscopic examination, and underwent high-resolution manometry and impedance (HRiM), and 24-h multi-channel intraluminal impedance and pH recording (MII/pH) in the digestive department of Beijing Anzhen Hospital and Beijing Chao-Yang Hospital between December 2014 and December 2016 were enrolled. Patients with other chronic active medical diseases (such as coronary artery disease, hypertension, malignancy, and diabetes mellitus) were excluded.

Patients with heartburn and a normal upper gastrointestinal endoscope exam, abnormal oesophageal acid exposure, and positive or negative symptom reflux association, were diagnosed with NERD. The diagnostic criteria for RH were all of the following: (i) the presence of retrosternal symptoms, including heartburn and chest pain, (ii) normal endoscopy and absence of evidence that eosinophilic o oesophagitis was the cause of the symptoms, (iii) absence of major oesophageal motor disorders (achalasia/oesophagogastric junction (EGJ) outflow obstruction, diffuse oesophageal spasm, jackhammer oesophagus, and absent peristalsis), and (iv) evidence of triggering of symptoms by reflux events despite normal acid exposure on pH or pH-impedance monitoring (response to anti-secretory therapy does not exclude the diagnosis). The criteria had to be fulfilled for 3 months prior to the beginning of the study, with symptom onset at least 6 months prior to diagnosis with a frequency of at least twice per week [3‐5].

A specially designed solid-state manometry catheter (Sandhill Scientific Inc., Highland Ranch, CO, USA) with 32 manometric sensors and four pairs of MII sensors, separated by 5-cm intervals, was used to assess oesophageal pressures and impedance with the patient in a supine position. The lower oesophageal sphincter (LES) was examined with distal circumferential manometric sensors. The catheter was positioned so that the pressure transducers were located across the upper oesophageal sphincter, oesophageal body, and LES, and the distal channels were in the stomach. Ten swallows with 5 mL normal (0.9%) saline solution were then performed at 30-s intervals.

The 2.1-mm outer diameter study catheter consisted of six electrode pairs for measuring intraluminal impedance (3, 5, 7, 9, 15, and 17 cm above the LES) and an antimony pH sensor 5 cm above the LES (Sandhill Scientific Inc., Highland Ranch, CO, USA). An impedance amplifier delivered an ultra-low current in a range of 1-2 kHz, with resulting current flow variations in response to intraluminal impedance changes (high impedance indicates gas or air; low impedance indicates liquid). Signals from the six impedance channels and the pH channel were recorded at 50 samples per second. The data were stored in an ambulatory recorder and saved on a 256-MB CompactFlash card. Event markers recorded the occurrence of symptoms, times of meals, and changes in body position. The study was performed on an outpatient basis after an overnight fast with the LES located by oesophageal manometry. The patients undertook HRiM and MII/pH with a 7-day washout for proton pump inhibitors and/or H₂ antagonists.

Oesophageal bolus clearance can be assessed by measurement of total bolus transit time by classifying swallows as complete bolus transit (if bolus entry occurs at the most proximal site and bolus exit points are recorded in all three distal recording segments) or as incomplete bolus transit (if bolus exit is not identified at any of the three distal recording segments), and in terms of the complete bolus transit rate. The distal contractile integral (DCI) of the distal segmental contraction is a parameter that integrates contractile pressure (mmHg), duration (s) of contraction, and the length of the smooth muscle oesophagus (cm). Distal oesophageal amplitude (DEA) is an average of the contraction amplitude at 5 and 10 cm above the LES. Integrated relaxation pressure (IRP) reports the mean EGJ pressure, which is measured with an electronic equivalent of a sleeve sensor for four continuous or non-continuous seconds of relaxation in a 10-s window following deglutitive UES relaxation. The parameters of the length of the lower oesophageal sphincter (LESL), the lower oesophageal sphincter pressure (LESP), the lower oesophageal sphincter residual pressure (LESRP), and the upper oesophageal sphincter pressure (UESP) were also measured [7, 8]. Ineffective oesophageal motility (IEM) was defined as at least 50% of swallows with a DCI below 450 mmHg∙s∙cm [9]. Fragmented peristalsis was defined as at least 50% of fragmented swallows (contractions with DCI > 450 mmHg∙s∙cm and break > 5 cm in the 20 mmHg isobaric contour) [9]. The parameters of DeMeester score, acid exposure upright (%), acid exposure recumbent (%), acid exposure total (%), bolus exposure upright (%), bolus exposure recumbent (%), bolus exposure total (%), proximal acid events, proximal nonacid events, proximal total events, distal acid reflux events, distal non-acid reflux events, and distal total reflux events were measured [10]. Symptoms were considered to be associated with reflux if they occurred within a 2-min window after the onset of the reflux episode [10]. The symptom index (SI) was considered positive if the value was 50% or more; symptom association probability (SAP) was considered positive if it was 95% or more [11, 12]. All parameters were measured using Bio View Analysis software (Sandhill Scientific, Inc., Highland Ranch, CO, USA).

A post-reflux swallow-induced peristaltic wave (PSPW) was defined as an antegrade 50% drop in impedance relative to the pre-swallow baseline originating in the most-proximal impedance site, reaching all distal impedance sites, and followed by a return to at least 50% of the baseline in the distal impedance sites (bolus exit). Post-reflux swallows that did not reach the distal impedance sites, or that occurred more than 30 s after the end of reflux episodes, were not considered. For each impedance-pH tracing, the number of refluxes followed within 30 s by a PSPW was divided by the number of total refluxes (manual calculation) to obtain the PSPW index [13].

Mean nocturnal baseline impedance (MNBI) was assessed from the most distal impedance channel during a night recumbency period. Three 10-min time periods (at around 1:00 AM, 2:00 AM, and 3:00 AM) were selected, and the mean baseline for each period was computed with the aid of the software. Time periods including swallows, refluxes, and pH drops were avoided. The mean of the three measurements was manually calculated to obtain the MNBI [14].

There were two groups in the study: Chinese NERD patients and RH patients. The diagnosis of acid exposure was according to the results of MII/pH, presenting an abnormal upright acid exposure time (≥6.3%), recumbent acid exposure time (≥1.2%), or total acid exposure time (≥4.2%) [10].

Categorical data are described as means ± standard deviation (SD). Data were analysed using the independent-samples t-test or χ ² test. A p-value < 0.05 was considered to indicate statistical significance. All data were analysed with the SPSS software (ver. 17.0, IBM Corp., Armonk, NY, USA).