Detection and Use of Nasal Nitrous Oxide and the Electronic Nose
Condition: Allergic Rhinitis; Non-Allergic Rhinitis; Nasal Polyps
MeSH terms: Rhinitis; Common Cold; Rhinitis, Allergic; Nasal Polyps
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): Nasal nitrous oxide; Electronic nose
Intervention type(s): Device; Device
Intervention description(s): Electrochemical device (NOVario Analizer FILT), to determine reference values of Nasal nitrous oxide.; To determine reference values of different patterns of specific volatile organic compounds with the electronic nose (Cyranose 320®).
Intervention MeSH terms: Nitrous Oxide
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Electronic nose; Nasal nitrous oxide; Allergic Rhinitis; Non-Allergic Rhinitis; Nasal polyps