Recent advances in cystic fibrosis

Abstract

Cystic fibrosis, one of the most common lethal inherited disorders in N. European and N. American populations, is characterized by the production of abnormally viscous mucous secretions in the lungs and digestive tract. The pathophysiological basis of the disease is unknown. However, during the last few years, rapid advances in molecular genetics and biochemical and physiological studies on cystic fibrosis epithelial cells have led to optimism that the cystic fibrosis defect will soon be identified. Current evidence suggests that the basic disturbance lies in altered regulation of protein secretion and electrolyte transport leading to an imbalance in composition of epithelial secretions in cystic fibrosis patients. Increasing knowledge of the mechanisms regulating production and secretion of mucins and movement of electrolytes across the cell membrane should lead to development of pharmacological manipulation(s) to correct the cellular abnormality. Ultimately, it is hoped that this will lead to the development of a rational treatment for cystic fibrosis patients.

The prevalence of nasal polyps in adults with cystic fibrosis

“…Cystic fibrosis is the most common fatal inherited disease among caucasians. It has an autosomal recessive mode of inheritance with an incidence of one in 2000 live births and a carrier risk of 5% 1 . Cystic fibrosis is a generalized exocrinopathy characterized by chronic pulmonary disease, pancreatic insufficiency and increased levels of sweat electrolytes.…”

Defective phosphorylation of a calmodulin-binding protein in cystic-fibrosis submandibular glands

“…A common abnormality has been demonstrated in CF epithelial tissues; thus protein secretion and Cl-transport have been shown to be defective in response to stimuli which act primarily by increasing cyclic AMP levels (McPherson & Dormer, 1987, 1988. Evidence suggests that the abnormality in CF cells lies distal to cyclic AMP formation (McPherson & Dormer, 1987, 1988.…”

“…A common abnormality has been demonstrated in CF epithelial tissues; thus protein secretion and Cl-transport have been shown to be defective in response to stimuli which act primarily by increasing cyclic AMP levels (McPherson & Dormer, 1987, 1988. Evidence suggests that the abnormality in CF cells lies distal to cyclic AMP formation (McPherson & Dormer, 1987, 1988. The demonstration, using patchclamp techniques, that apical-membrane Cl-channels on airway epithelial cells are opened by protein kinase A in control cells, but not in CF cells (Schoumacher et al, 1987;Li et al, 1988), indicated a defect in phosphorylation of a key regulator protein involved in secretion.…”