Cystic Fibrosis

Key Features

Essentials of Diagnosis

• Chronic or recurrent cough, sputum production, dyspnea, and wheezing

• Recurrent airways 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

• Pancreatic insufficiency, recurrent pancreatitis, distal intestinal obstruction syndrome, chronic hepatic disease, nutritional deficiencies, or male urogenital abnormalities

• Sweat chloride concentration > 60 mEq/L on two occasions

• Mutations in genes known to cause cystic fibrosis

General Considerations

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

• Autosomal recessive disorder due to mutations affecting a membrane chloride channel (the cystic fibrosis transmembrane conductance regulator, or CFTR)

• 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

• Common extrapulmonary manifestations

  • Steatorrhea

  • Diarrhea

  • Abdominal pain

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

• Other findings include

  • Digital clubbing

  • Increased anteroposterior chest diameter

  • Hyperresonance on percussion

  • Apical crackles

Differential Diagnosis

• Chronic obstructive pulmonary disease

• Asthma

• Alpha-1-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, S maltophilia, and B cenocepacia

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 CT is the test of choice to confirm bronchiectasis

Diagnostic Procedures

• Chloride sweat test reveals elevated sodium and chloride levels; two tests on different ...