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Cystic fibrosis (CF) typically first presents in childhood, but nearly 4 percent of patients are diagnosed as adults. About 34 percent of patients reach adulthood and nearly 10 percent live past the age of 30. The average life span for both male and female CF patients is 28 years. CF is characterized by chronic airway infection that leads to bronchiectasis and bronchiolectasis, exocrine pancreatic insufficiency and

Pathogenesis

Genetic Basis

CF is an autosomal recessive disease resulting from mutations in a gene located on chromosome 7. The prevalence of CF varies with the ethnic origin of a population. CF is detected in approximately 1 in 3000 live births in the Caucasian population of North America and northern Europe, 1 in 17,000 live births of

CftrProtein

The CFTR protein is a single polypeptide chain containing 1480 amino acids that appears to function both as a cyclic AMP-regulated Cl^- channel and, as its name

Epithelial Dysfunction

The epithelia affected by CFexhibit different functions in their native state; i.e., some are volume-absorbing (airways and intestinal epithelia), some are

Organ-Specific Pathophysiology

Lung

The diagnostic biophysical hallmark of CF is the raised transepithelial electric potential difference (PD) detected in airway epithelia. The transepithelial PD reflects components of both the rate of active ion transport and the resistance to ion flow of the superficial epithelium. CF airway epithelia exhibit both raised transport rates (Na⁺) and decreased ion

Gastrointestinal Tract

The gastrointestinal effects of CF are diverse. In the exocrine pancreas, the absence of the CFTRCl^- channel in the apical membrane of pancreatic ductal epithelia limits the function of an apical membrane Cl^--HCO₃^- exchanger to

Diagnosis

Because of the large number of CF mutations, DNA analysis is not used for primary diagnosis. The diagnosis of CF rests on a combination of clinical criteria and analyses of sweat Cl^- values. The values for the Na⁺ and Cl^- concentration in sweat vary with age, but

It is likely that DNA analyses will be performed increasingly in CF patients. Comprehensive genotype-phenotype relationships have not yet been established sufficiently for prognosis.

Clinical Features

Most CF patients present with signs and symptoms of the disease in childhood. Approximately 15 percent of patients present within the first 24 h of life with gastrointestinal obstruction, termed meconium ileus. Other common presentations within the first year or two of life include respiratory tract symptoms, most prominently cough and/or recurrent pulmonary infiltrates, and failure to thrive. A significant proportion of

Respiratory Tract

Upper respiratory tract disease is almost universal in CF patients. Chronic sinusitis is common in childhood and leads to nasal obstruction and rhinorrhea. The occurrence of

In the lower respiratory tract, the first symptom of CF is cough. With time, the cough becomes persistent and produces viscous, purulent, often greenish-colored sputum. Inevitably, periods of clinical stability are interrupted by "exacerbations," defined by increased cough, weight loss, increased sputum volume, and decrements in pulmonary

CF patients exhibit a characteristic sputum microbiology. Haemophilus influenzae and S. aureus are often the first organisms recovered from samples of lung secretions in newly diagnosed CF patients. P. aeruginosa is typically cultured from lower respiratory tract secretions thereafter. After repetitive antibiotic exposure, P. aeruginosa, often in a mucoid form, is usually the predominant organism recovered from sputum and may be present as several strains with different antibiotic sensitivities. Burkholderia (formerly Pseudomonas) cepacia has been recovered from CF sputum and is pathogenic. Patient-to-patient spread of certain strains of this organism indicates that infection control in the 

CF pulmonary disease is associated with many intermittent complications. Pneumothorax is common (>10 percent of patients). The production of small amounts of blood in sputum is common in CF patients with advanced pulmonary disease and appears to be associated

Gastrointestinal Tract

The syndrome of meconium ileus in infants presents with abdominal distention, failure to pass stool, and emesis. The abdominal flat plate can be diagnostic, with small intestinal air fluid levels, a granular appearance representing meconium, and a small colon. In children and young adults, a syndrome termed meconium ileus equivalent or distal intestinal

Genitourinary System

Late onset of puberty is common in both males and females with CF. The delayed maturational pattern is likely secondary to the effects of chronic lung disease and

Treatment

The major objectives of therapy for CF are to promote clearance of secretions and control infection in the lung, provide adequate nutrition, and prevent intestinal obstruction. Ultimately, gene therapy may be the

At present, the principal technique for clearing pulmonary secretions is a combination of breathing exercises and chest percussion. It should be stressed that regular use of these

Increased cough and mucus production are treated with antibiotics given by the oral route. Typical oral agents used to

A number of pharmacologic agents for increasing mucus clearance are being tested. N-acetyl-cysteine, which solubilizes mucous glycoproteins, has not been shown to have clinically significant effects on mucus clearance and/or lung function. Recombinant human DNAse, however, degrades the concentrated DNA in CF sputum, decreases sputum viscosity, and increases airflow during short-term administration. Long-term (6 months) DNAse treatment also increases the time between pulmonary exacerbations, although mild adverse effects have been noted. Most patients receive a therapeutic trial of DNAse to test for 

Inhaled beta-adrenergic agonists can be useful to control airways constriction. They achieve a short-term increase in airflow, but long-term benefit has not been shown. Inhaled

The chronic damage to airway walls reflects to some degree the destructive activities of inflammatory enzymes generated in part by inflammatory cells. To date, specific therapies

A number of pulmonary complications require acute interventions. Atelectasis is best treated with chest physiotherapy and antibiotic therapy. Pneumothoraces involving 10 percent or less of the lung can be observed without intervention. The use of chest tubes to expand collapsed, diseased lung often requires long periods of time, and sclerosing agents should be used with caution because of possible limitations for subsequent lung transplantation. Small-volume hemoptysis requires no specific therapy other than treatment of lung infection and assessment of coagulation and vitamin K status. If massive hemoptysis occurs, bronchial artery embolization can be successful. The most ominous complications of CF are