CFTR protein expression in cells from CF patients: correlation with clinical, functional, and inflammatory parameters.

Cystic fibrosis (CF) is the most common lethal autosomal recessive disorder in
the Caucasian population, with an overall birth prevalence in the Netherlands
of 1 in 4750 live births from 1974 to 1994. CF patients with a similar CFTR
gene mutation display a broad clinical spectrum, and gene modifiers only partly
explain these differences. Active transcription of the CFTR gene and CFTR mRNA
transcripts are detectable in a variety of epithelial cells (lung, nose,
intestine) and also in cells of non-epithelial origin. CFTR expression in human
immune cell subsets has been reported for macrophages, neutrophils, and T
cells. There are however no studies that compare levels of CFTR protein
expression in these different human immune cells, nasal epithelial cells or in
human alveolar macrophages or compare these CFTR protein expression levels with
clinical and inflammatory parameters.

Main objective is to assess CFTR protein expression in nasal epithelial cells
and in different peripheral blood immune cell subsets from CF patients with
different CFTR gene mutations.
Secondary objective is to correlate these expression levels with clinical
parameters (lung function, sputum culture, chest radiograph scoring systems),
functional tests measuring CFTR channel function (sweat chloride test, nasal
potential differences), inflammation measured in serum and sputum (including
different cytokines and chemokines), and functional testing of lymphocytes,
monocytes and granulocytes.
Third objective is to assess CFTR protein expression in alveolar macrophages
isolated from bronchoalveolar lavage fluid (BALF). CFTR expression levels will
be correlated with clinical parameters (lung function, sputum culture, chest
radiograph scoring systems), functional tests measuring CFTR channel function
(sweat chloride test, nasal potential differences), and inflammation measured
in BALF (cytokines and chemokines).

Cross-sectional observational study

Annual blood sampling, sputum sampling, and BALF obtained by bronchoscopy is
part of good clinical practice in children with CF. Nasal swabs are conducted
by the ear nose and throat specialist on a regular basis and are part of
standard care. There are no additional risks in obtaining nasal epithelial
cells by nasal swabs.