Chronic rhinosinusitis and nasal polyposis a GA2LEN cohort study

TITEL : Chronic rhinosinusitis and nasal polyposis a GA2LEN cohort study


Chronic rhinosinusitis is one of the most common health care problems, with
significant direct medical costs and severe impact on lower airway disease and
general health outcomes.
Rhinosinusitis remains a significant health problem with a considerable
socio-economic burden and is still increasing in prevalence and incidence. US
data of 1997 indicate a prevalence of app. 15% of chronic rhinosinusitis
patients (defined as having *sinus trouble* for more than 3 months in the year
before the interview) in the general population.(1) In the period from 1985 to
1992, the number of antibiotic prescriptions for sinusitis rose from 7.2
million to 13 million per year.(2) According to figures from IMS Health, an
internationally accepted information provider for the pharmaceutical and health
care industries, acute sinusitis was diagnosed 6.3 million times and chronic
sinusitis 2.6 million times in Germany, a European country with 81 million
inhabitants, over the course of one year (7/2000-6/2001), resulting in 8.5
million and 3.4 million prescriptions, respectively. The number of diagnoses of
*nasal polyposis* was approximately 221,000. (3)
In order to summarize the current knowledge of pathophysiology, as well as
guidelines for the therapeutic and diagnostic management of sinus disease,
position papers have recently been developed in the US (4) and Europe (5),
which also identify deficits in our understanding. (4)
Rhinosinusitis is a heterogeneous group of diseases, with different underlying
etiologies and pathomechanisms, and may represent an umbrella, covering
different disease entities. Rhinosinusitis is diagnosed based on symptoms and
duration of symptoms, clinical examination, nasal endoscopy and CT-scan.
However, the pattern of symptoms and signs is overlapping in all patients with
chronic sinus inflammation, whether they have formation of nasal polyps (NP) or
not (CRS It is currently not understood whether acute recurrent rhinosinusitis
necessarily develops into chronic rhinosinusitis, which then possibly gives
rise to polyp growth, or whether these disease entities develop independently
from each other. All of these items may be referred to *rhinosinusitis*,
meaning the *inflammation of the nose and the sinuses*; however, for clinical
and research purposes, a differentiation of these identities should be
preferred. For this purpose, we differentiate between acute rhinosinusitis
(ARS), chronic rhinosinusitis (CRS) without polyps and chronic rhinosinusitis
with nasal polyps (NP), and omit an ill-defined group of *hyperplastic chronic
rhinosinusitis*, which might be included in CRS, or represent an overlap
between CRS and NP.). As a result, all chronic sinus disease is considered as
one disease spectrum, *chronic rhinosinusitis*.
So far, nasal polyp formation in specific conditions such as cystic fibrosis
(CF) and allergic fungal sinusitis (AFS) can be differentiated as disease
entities, based on genetic defects in CF and a specific IgE-mediated immune
response to fungi in AFS respectively. For the majority of chronic sinusitis
cases, however, classification awaits further insights into pathomechanisms and
the introduction of appropriate disease markers. Such markers could possibly be
derived from 1) inflammatory cells, such as eosinophils and neutrophils, which
can be found in increased numbers in some forms of sinus disease, 2) from the
Th1/Th2 paradigm, possibly also involving T regulatory cells, and the cytokines
released from those cells, 3) from remodelling processes linked to fibrosis or
oedema formation, or 4) from innate or adaptive immunity products such as
toll-like receptors or immunoglobulins. Differences in some of these markers in
sinus disease versus nasal control tissue have been described (6), but these
have not proven useful to differentiate disease entities of CRS. For example,
interleukin (IL)-5, an eosinophil survival and differentiation factor, and
eosinophil-cationic protein (ECP), an indicator for eosinophil activation, have
been found to be significantly increased in NP versus controls. (7) Only
recently, differences in the expression of metalloproteinases and their
inhibitors could be demonstrated in CRS versus NP mucosal tissue. (8)
By characterizing the patients on the basis of clinical parameters, infectious
agents, inflammatory mechanisms(chemokines, cytokines), and remodeling
processes(growth factors), the term CRS will probably be further differentiated
into smaller disease entities, which might be treated differentially.

1. To integrate ENT specialists into the GA²LEN project in co-operations with
internal medicine, allergists and pneumologists.

2. To characterize patients with upper airway diseases on the basis of clinical
parameters, infectious agents, inflammatory mechanisms and remodeling processes.

3. To differentiate the term chronic rhinosinusitis further to smaller disease
entities based on clinical and biological parameters.

This cohort study is subdivided into two parts which will be performed
independently from each other. The first part encompasses a cross-sectional
study which will aim to differentiate chronic sinus disease.

The major burden of the study is the extra time for the patient, whcih is one
hour during visits that the patient is already in the hospital for regular
visits. None of the procedures here have major safety concerns.
Skin testing: Severe reactions are rarely if ever seen using this technique.
Centres will however be instructed to keep adrenaline available. Itching is a
common problem but disappears after 30 minutes.
Venesection: This may cause a little discomfort and can cause minor bruising.
All phlebotomists will be trained in aspects of safety relating both to
themselves and the patients.
collecting nasal secretion: minimally uncomfortable