Cystic Fibrosis (CF) is one of the most common life-threatening autosomal recessive diseases in the Western World, with a reported incidence rate of approximately 1 in every 2.000 to 5.000 caucasian newborns in most European countries. The gene mutation that plays an important role in the pathophysiology of CF is a mutation in the cystic fibrosis transmembrane conductor regulator (CFTR) gene on chromosome 7. Currently, 1890 mutations in this gene are known to be associated with CF, from which the F508 deletion is the most prevalent mutation. The CFTR gene codes for the CFTR protein which is present in the membrane of epithelial cells, and functions as an important regulator of the surface fluid in the airways. Mutations in this gene result in defective chloride secretion and excessive sodium reabsorption, which negatively impacts the airway surface fluid and impairs the mucociliary clearance. This may form the basis for the chronic bacterial airway infection and inflammation characteristic for CF, which results in irreversible lung damage.However, the pathophysiology of CF is not completely understood and the mechanism of acquisition and maintenance of bacterial infection in the CF airway is unclear. In addition, there is a poor correlation between genotype and phenotype, especially with the severity of lung disease. Thus, knowing which mutation causes CF is of little help in predicting the course of the disease.

The studies in this thesis were supported by grants from the Sophia CF research fund, the CF Trust of the Royal Children’s Hospital, Melbourne, Australia, the Dutch Cystic Fibrosis Foundation (NCFS), the Italian CF Fund (IERFC) and the Sophia research fund (SSWO)
G.P. Krestin (Gabriel) , H.A.W.M. Tiddens (Harm)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam

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