Genetics and pathophysiology, in Cystic Fibrosis (Oxford Respiratory Medicine Library) (2010).

Horsley AR

Oxford University Press

• Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians associated with early death
• Unaffected carrier frequency is 1:25 • Phe508del is the most common of over 1,500 mutations
• The gene encodes a transmembrane chloride conductance channel, the CFTR, which regulates chloride ion and water movements across the cell membrane
• CFTR is expressed throughout the body, and CF disease affects multiple systems, including major effects on the lung, pancreas and gastrointestinal systems
• Pulmonary disease is the most important cause of death and disability, resulting from chronic progressive suppurative lung disease
• Over-activation of the sodium (ENaC) channel in the lungs, caused by loss of CFTR-inhibition, results in dehydration of the airway surface fluid layer and consequent poor mucociliary clearance
• Retained secretions encourage bacterial adherence, chronic neutrophillic infection, and a vicious cycle of infection, inflammation and tissue destruction.