Abstract
Cystic fibrosis (CF) is a common, life-threatening, multisystemic, autosomal recessive
disorder. In the last few years, giant steps have been made with regard to the understanding
of CF pathophysiology, allowing the scientific community to propose mechanisms that
cause the myriad of CF clinical manifestations. Following the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989, the structure and function of the CFTR protein were described. Since
then, more than 2,000 variants of the CFTR gene and their impact on the amount and function of the CFTR protein have been reported.
The role of the CFTR protein as an ion channel transporting chloride and bicarbonate
and its repercussions on different epithelial cell-lined organs and mucus are now
better understood. Mechanisms behind susceptibility to infection in CF have also been
proposed and include abnormalities in the composition, volume and acidity of the airway
surface liquid, changes in the submucosal gland's anatomy and function, and deficiencies
in the mucociliary clearance system. Numerous hypotheses explaining the excessive
inflammatory response in CF are also debated and involve impaired mucociliary clearance,
persistent hypoxia, lipid abnormalities, protease and antiprotease disproportion,
and oxidant and antioxidant imbalance. The purpose of this review is to summarize
our current knowledge of CF pathophysiology, including significant historic discoveries
and most recent breakthroughs, and to improve understanding and awareness of this
fatal disease.
Keywords
cystic fibrosis - pathophysiology - CFTR - infection - inflammation - proteases -
oxidants - mucins
