Cystic fibrosis

Cystic fibrosis (CF) is the most common lethal inherited disease in causcasian populations in North American and most of Europe. It is estimated that as many as 5 percent of the population may be heterozygous for the CF gene. CF has not yet been defined as a specific genetic disorder with a known gene product. It is possible that more than one genetic defect may be responsible for the syndrome now recognized as CF. There is clearly a wide variation in clinical severity and even clinical presentation among different patients, although most observations are consistent with an autosomal recessive mode of inheritance. At present, the median survival age for patients born with CF is approximately 21 years. Clinically, CF is characterized by three major features: increased concentrations of sodium and chloride in the sweat, chronic obstructive lung disease with chronic bacterial infection, and, in 90 percent of the patients, exocrine pancreatic insufficiency. The latter is usually manifest from birth and is commonly thought to result from pancreatic ductal obstruction with consequent autodigestion of the secretory elements of the pancreas. The pulmonary component of CF is the most significant clinical aspect of the disorder and is responsible for at least 95 percent of the deaths. Patients with CF begin life with normal lungs, but soon develop evidence of hypersecretion of mucus. Chronic bacterial colonization and infection, characteristically with Staphylococcus aureus and/or Pseudomonas aeruginosa, soon follow. In most patients, the initial pathologic process begins in the bronchioles, with peribronchiolar inflammation and bronchiolar obstruction. In many infants, this process may be initiated or exacerbated by concurrent viral infection. Once infection has become established, the sequence of pathophysiologic events becomes less clear. As the disease progresses, larger airways become involved, with chronic inflammation progressing to bronchiectasis. Clinically, the bronchial secretions are increased in volume and viscosity, and are usually purulent. Mucociliary transport is decreased but not absent, and ciliary structure and beat (at least in vitro) appear normal. Patients develop a viscous cycle of airway obstruction leading to airway infection, which in turn leads to further obstruction. Eventually destruction and obstruction of airways progress to the point of irreversibility, and patients usually die in respiratory failure with cor pulmonale.