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ESSENTIALS OF DIAGNOSIS
Pulmonary disease: chronic or recurrent productive cough, dyspnea, and wheezing; recurrent airway infections or chronic colonization of the airways with H influenzae, P aeruginosa, S aureus, or Burkholderia cenocepacia; bronchiectasis and scarring on chest radiographs; airflow obstruction on spirometry.
Extrapulmonary disease: sinus disease; gastrointestinal disease (pancreatic insufficiency, recurrent pancreatitis, hepatobiliary disease, meconium ileus, and distal intestinal obstruction); genitourinary problems (male infertility and urogenital abnormalities)
Sweat chloride concentration > 60 mEq/L on two occasions.
Presence of two disease-causing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
Abnormal nasal potential difference.
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GENERAL CONSIDERATIONS
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Cystic fibrosis is the most common cause of severe chronic lung disease in young adults and the most common fatal hereditary disorder of Whites in the United States. It is an autosomal-recessive disorder affecting about 1 in 3000 Whites; 1 in 25 is a carrier. Cystic fibrosis is caused by abnormalities in a membrane chloride channel (the cystic fibrosis transmembrane conductance regulator [CFTR] protein) that results in altered chloride transport and water flux across the apical surface of epithelial cells. Almost all exocrine glands produce an abnormal mucus that obstructs glands and ducts and leads to tissue damage. In the respiratory tract, inadequate hydration of the tracheobronchial epithelium impairs mucociliary function. High concentration of extracellular DNA in airway secretions (due to chronic airway inflammation and autolysis of neutrophils) increases sputum viscosity. Over 1000 mutations in the gene that encodes CFTR have been described, and at least 230 mutations are known to be associated with clinical abnormalities. The mutation referred to as ΔF508 accounts for about 60% of cases of cystic fibrosis.
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Over one-third of the nearly 30,000 cystic fibrosis patients in the United States are adults. Because of the wide range of alterations seen in the CFTR protein structure and function, cystic fibrosis in adults may present with a variety of pulmonary and extrapulmonary manifestations. Adult patients with cystic fibrosis have an increased risk of osteopenia, arthropathies, and malignancies of the gastrointestinal tract, among others.
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A. Symptoms and Signs
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Cystic fibrosis should be suspected in an adult with a history of chronic lung disease (especially bronchiectasis), pancreatitis, or infertility. Cough, sputum production, decreased exercise tolerance, and recurrent hemoptysis are typical complaints. Patients also often complain of chronic rhinosinusitis symptoms, steatorrhea, diarrhea, and abdominal pain. Patients with cystic fibrosis are often malnourished with low body mass index. Digital clubbing (Figure 6–42), increased anteroposterior chest diameter, hyperresonance to percussion, and apical crackles are noted on physical examination. Sinus tenderness, purulent nasal secretions, and nasal polyps may also be seen. Nearly all men with cystic fibrosis have congenital bilateral absence of the vas deferens with azoospermia. Biliary cirrhosis and gallstones may occur.
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B. Laboratory Findings
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ABG studies often reveal hypoxemia and, in advanced disease, a ...