The Diagnostics of Extraesophageal Reflux With the Restech System
Condition: Nasal Diseases; Nasal Polyps; Laryngopharyngeal Reflux
MeSH terms: Gastroesophageal Reflux; Laryngopharyngeal Reflux; Nasal Polyps; Nose Diseases
Study type: Interventional

Summary: 
      The aim of the project is to define the frequency with which EER is present in patient with
      chronic rhinosinusitis (CHR). The measurement will be carried out with a 24-hour monitoring
      of the pH using the Restech system. This modern device is equipped with a narrow antimony
      probe. The sensor is able to record not only liquid but also aerosol reflux episodes. The
      second aim is to determine the relation among EER, CHR and asthma bronchiale. We will compare
      the presence of reflux in three different patient groups (1. CHR without nasal polyposis,
      without asthma bronchiale or ASA syndrome, 2. CHR with nasal polyposis, without asthma
      bronchiale or ASA syndrome, 3. CHR with nasal polyposis and asthma bronchiale and/or ASA
      syndrome). We expect to find a significantly more frequent presence of EER in patients with
      CHR and asthma bronchiale or ASA syndrome. In case our hypothesis is confirmed, it will be
      especially these patients(with a difficult to manage nasal polyposis) benefiting from the
      antireflux therapy.
    

Detailed description: 
      Introduction The problems of relation between some of the ENT diseases (posterior laryngitis,
      granulomas of the vocal cords, globus pharyngeus and others) and the extraesophageal reflux
      (EER), which is associated by the refluxate penetrating above the level of the upper
      oesophageal sphincter, has been studied more intensely especially during the last several
      years. The golden standard in the diagnostics of EER remains the dual-channel 24-hour
      pH-metry. The methodology of this procedure has been standardized in the past several years
      and differs significantly from the oesophageal pH-metry carried out by gastroenterologists
      (the upper probe is usually placed above the level of the upper oesophageal sphincter). The
      pH-metry enables us to monitor especially the impact of EER upon diseases of the oesophagus
      and hypopharynx. Non-existence of a simple and sensitive method was a barrier in a more
      detailed examination of the relations between EER and the more proximally located parts of
      the upper respiratory tract (nasopharynx, nasal cavity and paranasal sinuses, middle-ear
      cavity). The problem of "classical" pH-metry probes lies in the fact that unless the sensor
      is covered by a mucosa, it dries out and the record is not accurate.

      The Restech system was introduced two years ago, with the aim to improve the EER diagnostics
      in oropharynx and nasopharynx. The sensor of a very sensitive antimony probe is positioned at
      the tip of a 1,5 mm catheter, which is inserted through the nose behind the uvula (the exact
      positioning is controlled with the use of the illuminating end of the catheter). High
      sensitivity of this device enables to measure not only the pH of the liquid but also of small
      aerosol drops - so called aerosol reflux. The examination takes 24 hours, the data are being
      transferred wirelessly into a recording device. Normative data of a non-symptomatic group
      have also been defined. The advantages of this method, when compared with the dual-probe
      24-hour pH-metry are a higher sensitivity, easier accomplishment and better compliance of the
      patient population. However, a wider comparison data for different pathological conditions
      are still missing.

      EER is considered to be one of possible factors which may contribute to the onset or worsen
      existing chronic rhinosinusitis (CHR). It is a well-known fact that a part of the patients
      with CHR undergoing endonasal surgery suffer from an early recurrence of the disease.
      DelGaudio found out, using a 3-channel pH-metry, that adult patients with refractory or
      recurrent chronic rhinosinusitis experience a significantly higher number of nasopharyngeal
      refluxes, when compared to the patient population presenting no symptoms after surgical
      treatment; and recommends anti-reflux therapy as a part of treatment in patients with
      refractory chronic rhinosinusitis. The same view is supported by another author, Pincus, who
      in his clinical trial confirmed a good effect of proton pump inhibitors in the treatment of
      such patients. According to EPOS (European Position Paper On Rhinosinusitis and Nasal Polyps,
      2007), the relation between EER and chronic rhinosinusitis is currently at the level of a III
      degree evidence. EPOS also summarises the fact that patients suffering from chronic
      rhinosinusitis and pH-metry proven EER, present significantly more frequently alleviation of
      the symptoms following an anti-reflux therapy. In that respect, EPOS recommends further
      clinical investigation of this problem.

      It is possible to assume that the Restech system enables a more precise diagnostics of the
      patients (when compared to pH-metry), however this system has not been tested in the
      diagnostics of EER in patients with CHR, either in the Czech Republic or abroad. If the
      proposed relation is confirmed, it will mean a dramatic change in the process of treatment in
      a part of the CHR patients, suffering at the same time from EER ("more urgent" recommendation
      of anti-reflux therapy, especially in patients with recurrent and refractory CHR).

      It has been proved in the past that a part of the patient population with difficult to
      control asthma bronchiale also suffers from EER, and that these patients profit greatly from
      a treatment using proton pump inhibitors. Also a part of the patients with CHR suffers from
      asthma bronchiale or a complete ASA syndrome. It is possible to assume that EER, having a
      negative impact upon the asthma bronchiale, may have a similar negative effect upon CHR. The
      mutual interrelations among EER, CHR and asthma bronchiale have not been thoroughly studied;
      one of the aims of the proposed project is also to explore these relations.

      Aims of the project

        -  to determine how often is EER present in the patient population with CHR

        -  to compare the occurrence of EER in three groups of patients

             1. CHR without nasal polyposis, without asthma bronchiale or ASA syndrome

             2. CHR with nasal polyposis, without asthma bronchiale or ASA syndrome

             3. CHR with nasal polyposis and asthma bronchiale and/or ASA syndrome

      Working hypotheses

        1. A part of the patients with CHR present with a significant pathological EER penetrating
           into nasopharynx (significantly higher number of EER episodes, when compared with
           asymptomatic population)

        2. EER is more frequent in patients with CHR and concomitant asthma bronchiale or ASA
           syndrome

      Methodology The project is designed as a prospective study which is in compliance with the
      principles and policies of the Helsinki Declaration and has been approved by the Ethics
      Committee.

      Patients: The patients will be enrolled into the study at the rhinology out-patient part of
      the ENT department of the University Hospital Ostrava.

      A total of 90 patients will be enrolled into the study within 4 years: 30 patients suffering
      from CHR without nasal polyposis, without asthma bronchiale or ASA syndrome, 30 patients
      suffering from CHR with nasal polyposis, without asthma bronchiale or ASA syndrome, and 30
      patients suffering from CHR with nasal polyposis and asthma bronchiale and/or ASA syndrome
      Inclusion criteria: 1/ age (18-60 years), 2/ signing of the informed consent. Entry
      examination: Patients enrolled into the study will be asked to complete a questionnaire (age,
      sex, body weight, body height, smoking habits, asthma bronchiale or ASA syndrome, the period
      of treatment for CHR, the number of endonasal surgeries in the past), and further will
      complete the Reflux symptom questionnaire (questionnaire used to determine the symptoms
      typical for EER), Reflux finding score (findings in the larynx typical for EER) and the
      degree of polyposis (1.-3.) will be recorded.

      24-hour monitoring of the nasopharyngeal pH using the Restech system: Description of the
      Restech device please see "Introduction". The measure parameters to prove EER in the
      nasopharyngeal area: the number of EER episodes, fractional time below pH 5.5 and RYAN
      composite score.

      Data collection, analysis of data and proposal of the statistical processing The statistical
      processing will be carried out by Ing. Hana Tomášková, PhD. from the Institute of
      Epidemiology and Public Health, Medical Faculty of the Ostrava University.

        1. The percentage of patients with EER will be defined from the overall number of CHR
           patients and individually for each group.

        2. We will determine whether there exists a significantly higher percentage of patients
           with EER in any of the three examined groups, when compared with the other groups.

        3. Other independently assessed factors in the group of patients with proven EER and the
           group without proven EER will be the age, sex, BMI, smoking habits, Reflux symptom
           index, Reflux finding score, asthma bronchiale or ASA syndrome, the length of CHR
           treatment, the number of endonasal surgeries in the past and the degree of nasal
           polyposis.

      The method of descriptive statistics will be used for statistical processing (arithmetic
      mean, standard deviation, frequency tables), X2 test, Fisher's exact test, analysis of
      variance (ANOVA), OR calculation (odds ratio) with 95% confidence intervals and logistic
      regression. The statistical tests will be assessed on the significance level of 5%. The
      statistical analysis will be carried out with the Stata v. 10 programme. We will use the MS
      Excel programme for data collection.

      Discussion Measurement of pH with the Restech system is a new and sophisticated method which
      has been introduced into the clinical practice in the course of the past two years. The first
      normative data and composite RYAN score have already been defined for healthy population
      (please see Literature). Now it is necessary to verify the correlations with symptoms and
      clinical findings in different patient groups, which may be worsened by EER. One of such
      patient groups are also patients with CHR. There are just a few sparse publications in the
      world literature (DelGaudio, Pincus) examining the relation between EER and CHR with the use
      of pH-metry. These studies suggest the fact that EER may be considered a negative prognostic
      factor from the point of view of an early recurrence of nasal polyposis after an endonasal
      surgery. Also EPOS recommends further studies to be conducted regarding this topic. The aim
      of the proposed work is to define, using the measurement of nasopharyngeal pH with the
      Restech system (which is more accurate and sensitive than pH-metry), how often is a
      pathological EER present in patients with CHR. At the same time we will determine the
      relation among EER, CHR and asthma bronchiale. A clinical trial such as this does not exist
      in the world literature so far. In case we confirm the relation between CHR and EER, the
      clinical impact will be significant, taking into consideration the number of patients with
      CHR.

      Benefits of the project In case we confirm the hypothesis that EER is significantly more
      present in patients with CHR when compared to the common population, it is possible to expect
      that the antireflux therapy may be introduced into the treatment protocol of these patients.
      The presumption is such that the anti-reflux treatment will alleviate the patients´ symptoms
      (nasal patency, secretion), and possibly also decrease the number of recurrences and
      necessary reoperations. This will decrease the risks related to surgical procedures and
      improve the quality of life of these patients.
    

Intervention name(s): pH monitoring (Restech)
Intervention type(s): Device
Intervention description(s): see in "detail description of the study" part of the protocol
Other intervention name(s): oropharyngeal pH monitoring using Restech system
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: chronic rhinosinusitis; extraesophageal reflux; Restech system; antireflux therapy