Allergic Rhinitis Clinical Trial
Official title:
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.
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.
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