Phenotypes of Adults with Non-atopic Asthma; Mechanisms and Aetiology

Non-atopic or intrinsic asthma is a heterogeneous condition that is less well
understood than the classic allergic asthma that usually starts in childhood.
Non-atopic asthma is often more severe, less responsive to therapy and more
likely to result in fixed airflow limitation. Several clinical subtypes of
non-atopic asthma have been described, but it is unknown whether these are
associated with distinct types of airway inflammation, responses to therapy or
disease outcome.
Sinus disease is supposed to be an important factor complicating asthma
control, especially in non-atopic patients. However, the relationship between
inflammation in upper and lower airways in non-atopic asthma is unclear. In
addition, it is unknown whether non-invasive measurements of exhaled breath
might predict the extend of inflammation in upper and lower airways in patients
with non-atopic asthma.
Meticulous characterization of subjects with non-atopic asthma and phenotyping
of the disease by linking clinical, functional and molecular markers seems to
be critical for further understanding of the underlying pathophysiological
mechanisms. This will hopefully lead to phenotype-specific therapies that might
improve the outcome in this group of patients.

Study 1: The objective of this study is to thoroughly characterize a large
group of patients with non-atopic asthma clinically, functionally and with
respect to inflammatory parameters and define 3-4 major phenotypes of this
disease using unbiased cluster analysis.

Study 2: In this second part we will investigate whether levels of nitric oxide
(NO) in exhaled air are related to inflammatory processes in upper or lower
airways in non-atopic asthma.

Study 3: In the third part we will determine the diagnostic accuracy of the
electronic nose (eNose) in establishing the sensitivity, specificity, positive
and negative predictive value for detecting sinus disease in non-atopic asthma

Study 1: This will constitute the baseline project of a prospective
longitudinal follow up study of a large cohort (n=200) of patients with
non-atopic asthma. Inclusion period: Oct 2009-Jan 2012.


Study 2: a cross-sectional analysis will be performed to determine the
relationship between levels of exhaled NO, the type of lower airway
inflammation and the extent of nasal sinus disease in 200 patients with
non-atopic asthma.

Study 3: the potential of the electric nose to discriminate non-atopic asthma
patients with and without sinus disease will be prospectively investigated by
cross-sectional comparison between groups. In this part we will use results
obtained in a study where the eNose was trained to develop an algorithm to
discriminate patients with confirmed sinus disease from controls (AMC).

The burden associated with these studies includes *.. 2 hospital visits, during
which different measurements will be done. An interview, physical examination,
routine blood tests and lung function tests will be performed. Also an exhaled
nitric oxide measurement and exhaled volatile organic compounds analysis
(electronic nose) will be done.
All patients will perform sputum induction (for cell counts and pathogen
detection) which has shown to be well tolerated even by severe asthmatics in
previous studies.
All patients will be submitted to CT-scanning of the nasal sinuses and nasal
endoscopy by an ENT-specialist. The risk of and discomfort caused by these
procedures is small.

The results of these studies may be important for the group of non-atopic
asthmatic patients, as it will identify different subtypes of patients and
unravel the underlying mechanisms. This will hopefully give the clinician
support to diagnose different types of non-atopic asthma and lead to
phenotype-specific therapies that might improve outcome in this group of
patients. Hereby it might also help to reduce the personal and socioeconomic
burden of the disease.