Detection and Use of Nasal Nitrous Oxide and the Electronic Nose (EPONA)

February 12, 2020 updated by: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

AssEssment and New Perspectives on Pathophysiogenesis, detectiOn and Use of NAsal Nitrous Oxide and the Electronic Nose (EPONA Project)

Introduction: Rhinitis, sinonasal polyposis (SP) and asthma are diseases whose pathogenesis is based on inflammation. This will determine the presence of disease, its evolution and its treatment. It is therefore very important to develop and validate methodologies that allow us to noninvasively detect inflammation of the airways. Thus, just as exhaled nitric oxide (FeNO) has been studied as an important non-invasive marker of inflammation of the lower airways, nasal nitric oxide (nNO) may be a good marker of nasal inflammation. Furthermore, the electronic nose is an electronic nanosensor device capable of detecting specific volatile organic compounds (VOCs) that can be used as a non-invasive biomarker of biochemical processes in different diseases whose pathophysiology is also based on inflammation.

Objective: To determine reference values of nNO and different patterns of VOCs in healthy individuals, individuals with allergic rhinitis (AR) and non-allergic rhinitis and individuals with SP and asthma.

Methodology: Prospective, controlled study. Four groups will be included: Healthy subjects, patients with AR, non-allergic rhinitis and patients with SP and asthma (n=252). Prick-test to pneumoallergens will be performed. Determination of FeNO, nNO, lung function tests, measurement of VOCs by the electronic nose and blood samples will be taken. Bilateral nasal endoscopy and sample collection using the technique of brushing of mucosa and the placement of filter papers, for the study of nasal cytology and mediators of inflammation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Assessment of nasal and bronchial inflammation:

Rhinitis (allergic and non-allergic), SP and asthma are diseases that are characterized by processes whose pathogenesis is based on inflammation. Inflammation of the airways can be assessed directly or indirectly. The techniques for assessing inflammation directly can be divided into invasive techniques and non-invasive techniques.

Within invasive techniques we include those which require nasal or bronchial endoscopy such as biopsy. However, the applicability of these invasive methods has many limitations because they are not without risks and/or complications. They also require considerable experience to implement. It is therefore very important to develop and validate new methods that allow us to non-invasively detect inflammation of the upper and lower airways.

Nitrous oxide (NO): Is synthesized from the amino acid L-arginine by the action of the enzyme nitric oxide synthase (NOS). Three isoforms of this enzyme are known: nNOS or NOS1, which predominates in nervous tissue; iNOS, inducible NOS or NOS2, induced by an agent that activates the immune system; and eNOS, endothelial NOS or NOS3, constituent of the vascular endothelium. Since iNOS is found in different cells of the respiratory tract and is induced by various inflammatory cytokines, NO is considered to be an excellent marker for airway inflammation. Thus, just as exhaled nitric oxide (FeNO) is considered a good non-invasive marker of inflammation of the lower airways, nasal nitric oxide (nNO) potentially appears be a good marker of nasal inflammation.

Nasal nitric oxide (nNO): Some authors describe reference values for nNO up to one hundred times higher than those for FeNO. However, until now normal levels of nNO in different nasal diseases and in healthy individuals have not been established because the published results vary widely. Dotsch et al. in 1996 published a series of 67 healthy subjects in which they found mean nNO values in a healthy population of 96±47 ppb. A year later Ferguson studied 82 healthy patients and published mean normal values of nNO of 1197±361 ppb. Additional papers were published subsequently, but the results remained quite diverse.

As for the reference values in patients with rhinitis, data published so far are also contradictory. Some authors show that nNO is higher in patients diagnosed with rhinitis, especially in patients with AR. However, other studies have not observed differences in levels of nNO in patients diagnosed with rhinitis compared to the normal population.

The electronic nose: Is a new technique which is based on the detection of VOCs present in the gas phase of the human respiration and that can be detected by chromatography and mass spectrometry sensors. It consists of a device made up of several nanosensors that when exposed to volatile particles undergo specific changes in their electrical resistance, resulting in a pattern or profile of VOCs by logarithmic regression. These VOC patterns can be used as non-invasive biomarkers of several biochemical processes that occur in different diseases whose pathogenesis is based on inflammation. For example, in diseases of the airways they have been used successfully in comparing patterns of VOCs in patients with chronic obstructive pulmonary disease (COPD) and asthma. This technique's potential applicability in biomedicine is enormous.

In short, both measuring nNO and determining patterns of VOCs by the electronic nose are non-invasive methods that can help in the diagnosis and monitoring of certain respiratory diseases. However, in the case of nNO currently available studies show very different and conflicting results and in the case of the determination of VOCs by electronic nose there are very few papers published to date. It is therefore vital to design a study that allows us to clarify the potential utility of non-invasive markers of inflammation such as determination of nNO and determination of the different patterns of VOCs by electronic nose in healthy patients, in patients diagnosed with AR and non-allergic rhinitis and in patients with associated SP and asthma.

Working Hypothesis: Rhinitis, SP and asthma are prevalent diseases that cause considerable morbidity. Since the substrate of these diseases lies in inflammation, our group of investigators believe that the study of inflammation is one of the most interesting aspects for assessment and management of these diseases. Similarly to how measuring FeNO is being used as a good marker of bronchial inflammation, measuring nNO and determining patterns of VOCs by the electronic nose could also be two good non-invasive markers of upper and/or lower (in the case of VOCs) airway inflammation. However, although in recent years there have been some studies on the origin, function and utility of measuring nNO and the use of the electronic nose in respiratory disease, there are still many questions that remain in reference to these two techniques.

Study Type

Interventional

Enrollment (Actual)

139

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, 08025
        • Lorena Soto-Retes

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion criteria:

Sample of healthy individuals: Non-atopic individuals will be considered when skin prick skin tests with a standard battery of pneumoallergens are negative.

  • Individuals with nasal endoscopy not showing inflammatory lesions or anatomic abnormalities and who have an acoustic rhinometry compatible with normal values.
  • No sign of any acute infectious process during the four weeks preceding the study.
  • Signed informed consent.

Sample of individuals with Allergic Rhinitis: Atopic patients sensitized by skin prick testing and specific IgE determination to at least one perennial allergen.

  • Patients with symptoms compatible with persistent moderate or severe AR as rated by the ARIA 2008 guide of at least two years of evolution.
  • No acute infectious process during the four weeks preceding the study.
  • Signed informed consent.

Sample of individuals with non-allergic rhinitis: The subject will be considered non-atopic when skin prick skin tests with a standard battery of pneumoallergens are negative.

  • Patients with symptoms of sneezing, watery rhinorrhea, nasal itching and/or nasal obstruction of at least two years evolution.
  • No acute infectious process during the four weeks preceding the study.
  • Signed informed consent.

Sample of individuals diagnosed with Sinunasal Polyposis and asthma: Patients diagnosed with asthma by clinical and lung function tests.

  • SP patients diagnosed by performing nasal endoscopy and CT of the paranasal sinuses.
  • Could be non-atopic patients or present any concomitant allergic diseases.
  • No acute infectious process during the four weeks preceding the study.
  • Signed informed consent.

Exclusion criteria for all groups:

  • Smoker with history of more than 10 pack-years.
  • Pregnancy.
  • Having been treated with nasal or systemic drugs that may alter nasal resistance (vasoconstrictors, anticholinergics, corticosteroids, antihistamines, immunosuppressants and/or immunomodulators) during the past three weeks.
  • History of nasal surgery.
  • Having an autoimmune or inflammatory systemic disease.
  • Having an established diagnosis of intrinsic or extrinsic asthma (except polyposis group).
  • Individuals with pathological nasal endoscopy.
  • Suffering from a neoplastic disease.
  • Having been treated with nasal or systemic drugs that may alter nasal resistance (vasoconstrictors, anticholinergics, corticosteroids, antihistamines, immunosuppressants and/or immunomodulators) during the past three weeks.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NON_RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Nasal nitrous oxide
Mesurement of Nasal nitrous oxide in all groups: allergic rhinitis, non-allergic rhinitis, nasosinusal polyps and healthy group
Device: Nasal nitrous oxide
Electrochemical device (NOVario Analizer FILT), to determine reference values of Nasal nitrous oxide.
Active Comparator: Electronic nose
Measurement with the Electronic nose in all groups: allergic rhinitis, non-allergic rhinitis, nasosinusal polyps and healthy group.
Device: Electronic nose
To determine reference values of different patterns of specific volatile organic compounds with the electronic nose (Cyranose 320®).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Values of nNO measure as parts per billions (ppb)
Time Frame: 12 months
12 months
Values of the electronic nose measure as volatile organic compounts (VOCs)
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Collaborators

Sociedad Española de Neumología y Cirugía Torácica
Universitat Autonoma de Barcelona
Sociedad Española de Alergología e Inmunología Clínica

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

March 2, 2015

First Submitted That Met QC Criteria

June 17, 2015

First Posted (Estimate)

June 22, 2015

Study Record Updates

Last Update Posted (Actual)

February 13, 2020

Last Update Submitted That Met QC Criteria

February 12, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIBSP-ONA-2011-146

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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