History of Cystic Fibrosis

A western blot to detect CFTR protein from different plasmid constructs.

Cystic fibrosis (CF) was first recognised over 400 years ago in Germany and is the most common autosomal recessive disorder in Caucasians (Berkow et al., 1998). It is a hereditary disease that causes certain glands to produce abnormal secretions, the most important of which affect the digestive tract, the pancreas and the airway epithelia (Hodson & Geddes, 1995).

The basic defect in CF is a decrease in chloride conductance across apical membranes accompanied by an increase in the uptake of sodium ions. Studies showed that this phenotype persisted in cultured epithelial cells indicating a specific defect in these cell types (Wright & Morton, 1968). Patch clamp analysis showed that the defect was due to the failure of an outward chloride channel to respond to phosphorylation by cyclic adenosine monophosphate (cAMP) dependent protein kinase (PKA) or to protein kinase C.

In the CF patient the result is epithelial dysfunction which affects the genitourinary tract, the pancreas, sweat glands but most significantly the lungs and airway epithelia. Increased cellular chloride and sodium concentration leads to the production of abnormal salty mucus secretions from the cells. The viscous mucus reduces the capacity of the lungs and increases the frequency of infection.

This leads to a proliferation of neutrophils and leucocytes in the lung and the immune response mediated by these cells increases the viscosity of the airway interfaces even more and contributes to the lung damage (Hodson & Geddes, 1995).