The effect of nasal provocation on clinical response and nasal inflammatory parameters in nonallergic rhinitis, mixed rhinitis and allergic rhinitis patients versus healthy individuals

Chronic rhinitis is a common disorder, that can have great impact on quality of
life of patients. The pathophysiology can be divided into several subgroups.
Beside infectious and allergic rhinitis, nonallergic rhinitis forms an
important entity within rhinitis. Patients have symptoms that mimic allergic
rhinitis, such as rhinorrhea, nasal blockage and sneezing, of which the
definite pathophysiology has not been decribed. The diagnosis is largely based
on exclusion criteria. It has been suggested that the pathophysiologic or
pathogenic origin of nonallergic rhinitis has its origin at RNA level. Since
the nasal symptoms mimic those of allergic rhinitis, but triggering agents of
the symptoms differ largely, an adequate comparison between these groups, would
give better insight into the pathophysiology of nonallergic rhinitis.
Characterization of the phenotype of nonallergic rhinitis would help to better
understand the pathophysiology, diagnosis and management.

By a chemical, physiological and IgE-mediated nasal provocation test, nasal
responses will be provoked in different patientgroups. The clinical response
will be measured by visual analogue score, rhinitis symptomscore, peak nasal
inspiratory flowmetry and nasal nitric oxide measurement. The local response
will be measured by the quantification of mediators of inflammation in the
nasal secretion. Based on these responses, phenotypes of the different
subgroups. will be defined.
At RNA-level a baseline genetic expression profile of the epithelium for
mediators of inflammation and rhinitis will be determined by micro-array
technology.
We will compare patients from the nonallergic rhinitis subgroup to allergic
rhinitis patients, mixed rhinitis patients and healthy subjects.

This will be an observational study with cross-over design. All subjects will
visit the ear-, nose- throat department at 4 occasions. The first visit will be
a screening visit with baseline measurements and the nasal biopsyprocedure.
Then the three provocationvisits will take place in random order. Each
provocation will be done with a different nasal trigger. The agents that will
be used as a nasal trigger are nasal capsaicinspray, cold dry air and
housedustmiteextract. On various timepoints after provocation, clinical
reaction and local nasal inflammatory reaction will be determined by VAS score,
nasal symptom score, peak nasal inspiratory flow measurement, nasal NO
measurement and nasal secretion.

The four studygroups will undergo equal interventions. During the
provocationvisits, nasal provocations will take place with three different
entities. The provocation with capsaicin nasal spray will be performed in 4
increasing dosages: placebo, 0.5 microgram, 5.0 microgram and 10.0 microgram.
The cold dry air provocation will be performed in the next increasing dosages:
12.5 L, 25 L, 50 L, 100 L, 200 L and 400 L. The provocation with housedustmite
will be performed, using the following increasing dosages of Der-P-1
housedustmite extraction in aqueous solution: Placebo, 100 BU, 1000 BU and
10.000 BU

Patients with rhinitis cease the use of their nasal medication within one month
before participation. 48 Hours before each studyvisit, they do not take
antihistamines. There is a chance of a considerable increase of their rhinitis
symptoms. If abstinence from their medication is not possible, subjects cannot
be included in this study.
Subjects visit the ENT-department at four occasions of approximately 2 hours
each. In 40 subjects, nasal biopsies will be taken. The complication of nasal
biopsies is epistaxis.The incidence of epistaxis after nasal biopsies is
reported as being less than 5% and of moderate severity. In case epistaxis
occurs, treatment will consist of local application of Xylometzoline 0.01%, or
if necessary, a dissolvable nasal tampon will be placed. There will not be a
definitive change of the nasal mucosa after biopsy; complete healing will
occur.