Cystic Fibrosis

Key Features

Essentials of Diagnosis

• Pulmonary disease

  • Chronic or recurrent productive cough, dyspnea, and wheezing

  • Recurrent airway infections or chronic colonization of the airways with

    • Haemophilus influenzae

    • Pseudomonas aeruginosa

    • Staphylococcus aureus

    • 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

    • Distal intestinal obstruction

  • Genitourinary problems

    • Male infertility

    • 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

General Considerations

• Most common fatal hereditary disorder of Whites in the United States

• 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

• At least 1000 mutations to the CFTR gene are described, with "ΔF508" accounting for approximately 60% of cases

• Pathophysiology results from production of an abnormal mucous in exocrine glands, which leads to tissue destruction and, in the respiratory tract, impairs mucociliary clearance

• Variety of mutations is reflected in wide range of pulmonary and nonpulmonary manifestations

Demographics

• Affects 1 in 3200 Whites; 1 in 25 is a carrier

Clinical Findings

Symptoms and Signs

• Disease should be suspected in young adults with a history of chronic lung disease, pancreatitis, or infertility

• Productive cough, decreased exercise tolerance, and recurrent hemoptysis are typical

• 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

• Other findings include

  • Digital clubbing

  • Increased anteroposterior chest diameter

  • Hyperresonance on percussion

  • Apical crackles

• Nearly all male patients have congenital absence of the vas deferens with azoospermia

• Biliary cirrhosis and gallstones may occur

Differential Diagnosis

• Chronic obstructive pulmonary disease

• Asthma

• α₁-Antiprotease deficiency

• Bronchiolitis

• Celiac disease

• Chronic sinusitis

Diagnosis

Laboratory Tests

• Arterial blood gases reveal hypoxemia, with compensated respiratory acidosis in advanced disease

• Pulmonary function tests

  • A mixed obstructive and restrictive pattern

  • Reduced FVC, airflow rates, and total lung capacity

  • Air trapping and reduced diffusion capacity are common

• Genotyping, measurement of nasal membrane potential difference, semen analysis, or assessment of pancreatic function can play a role in diagnosis

• Sputum cultures

  • Frequently show S aureus and P aeruginosa

  • Occasionally show H influenzae, Stenotrophomonas maltophilia, and Burkholderia cepacia

Imaging Studies

• Hyperinflation is seen early on chest radiographs

• Peribronchial cuffing, mucus plugging, bronchiectasis, atelectasis, small rounded peripheral opacities, and increased interstitial markings are common

• High-resolution ...