Cystic Fibrosis (CF) is the most common fatal hereditary disease among Caucasians, affecting an estimated 70,000 people worldwide. CF is caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR), a protein that acts as a chloride channel. Over 1,900 mutations have been described in the CFTR gene, the most common of which is ÄF508. The disruption of chloride and sodium transport results in dehydration of mucus secretions in exocrine tissues, mainly the respiratory tract, pancreas, gastrointestinal tract, and sweat glands. The most debilitating consequence is the viscous mucus blocking the airways, leading to recurring cycles of obstruction, inflammation and chronic lung infection, frequently involving Pseudomonas aeruginosa. Severe pulmonary dysfunction is the usual cause of death in CF.
Although considerable progress has been made in understanding the pathogenesis of CF, the connection between CFTR dysfunction and the disease manifestations is not completely understood, especially with regards to the abnormal immuno-inflammatory response in the lung, an enigmatic pathogenic pathway responsible for most of morbidity and mortality in patients with CF.