Pilot study: Biomarkers for diagnosis of neutrophil inflammatory/ allergic asthma

About 10% of all asthmatics have severe, instable asthma and are
steroid-resistant. Severe, instable asthma is associated with neutrophil
recruitment and T helper (Th) 17 chemokine overexpression in bronchial
biopsies. Phenotyping of patients is important to optimize therapy and disease
outcome in an early stage. In clinical practise, for patients with severe
asthma who show an inadequate response to standard therapy, treatment with
macrolide antibiotics is considered.
In the Netherlands, asthma affects up to 3.5% of the adults and 4% of the
children below the age of 15 yrs. In 2007 the overall health expenditure was ¤
300 million. Half of these costs involve medication, i.e. combination
preparations (a long-acting-sympathomimetic agent with inhaled
corticosteroids). The annual direct medical expenditures and indirect
nonmedical costs range from around ¤500 for stable asthma to ¤2281 for unstable
asthma. Since unstable asthma burdens on overall health costs, early phenotypic
classification of severe asthma can guide the choice of the most appropriate
therapy with a reduction of exacerbations and health costs. However, at this
moment routine non-invasive diagnostic tests for severe neutrophil inflammatory
asthma are not available.

The aim of this pilot study is to establish Th1/Th2/Th17 patterns in healthy
controls by analysing cytokine concentrations in nasal fluid (nasal wash and
cotton wool method), saliva and blood. This will be done in order to give an
estimation about the expected values in a healthy population and the biological
variability of cytokines involved in the Th1/Th2/Th17 route. Furthermore it
will give information about the correlation in these patterns between nasal
fluid, saliva and blood.
Results of this pilot study will be used to start the main project; i.e. to
validate these potential biomarkers for the diagnosis of neutrophil allergic
asthma by measuring these analytes in patients suffering from severe, instable,
neutrophilic, allergic asthma and eosinophilic asthma. The METC application for
this main project will be send in at a later point in time.

Blood, saliva and nasal lavage of healthy subjects will be collected.
Th1/Th2/Th17 patterns in these fluids will be determined measuring cytokine
levels by flowcytometry.

Sampling will take place according to standard procedures of nasal fluid,
saliva and blood sampling. Risks of participation include the regular risks
involved in the sampling procedures; i.e. pain and bruises (for blood
sampling), irritation and a dry feeling in the nose (for the collection of
nasal fluid).