Cystic Fibrosis

Descriptive text is not available for this imageBASICS

DESCRIPTION

Cystic fibrosis (CF) is an inherited autosomal recessive disorder, characterized by chronic obstructive lung disease, pancreatic exocrine insufficiency, and elevated sweat chloride concentration.

ALERT
  • Due to variability in presentation, the most common pitfalls are failure to diagnose and initiate therapies in a timely manner. Earlier detection has become easier with the incorporation of the newborn screen and increasing accessibility of genetic testing.
  • Diagnosis may be delayed in patients with mild or atypical symptoms.

EPIDEMIOLOGY

  • Most common lethal inherited disease in the Caucasian population
  • Carrier frequency of mutations in the CF transmembrane conductance regulator (CFTR) gene
    • 1:29 in European-Americans
    • 1:49 in Hispanics
    • 1:53 in Native Americans
    • 1:62 in African Americans
    • 1:90 in Asians

Prevalence

  • 1:3,300 in European-Americans
  • 1:9,500 in Hispanics
  • 1:10,900 in Native Americans
  • 1:15,000 in African Americans
  • 1:35,000 in Asians

RISK FACTORS

Genetics

CFTR gene

  • Located on the long arm of chromosome 7
  • Most common mutation results in deletion of phenylalanine at position 508 in the CFTR glycoprotein.
  • The Δ508 mutation occurs in ~66% of CF patients.
  • >2,000 mutations have been reported in the CFTR gene.
  • Presence of gene modifiers may cause incomplete phenotypic presentations.

GENERAL PREVENTION

Prepregnancy carrier detection

PATHOPHYSIOLOGY

  • CFTR
    • Membrane glycoprotein, which functions as a cyclic AMP–activated chloride channel at the apical surface of epithelial cells
    • An abnormality in CFTR results in defective chloride conductance.
    • May have other roles in the regulation of membrane channels and the pH of intracellular organelles; may affect cell apical sodium channel regulation
    • CFTR abnormalities may act as binding sites for Pseudomonas aeruginosa, promoting proinflammatory responses in the lung.
  • In the respiratory system
    • Increased mucus viscosity
    • Early bacterial colonization despite a robust neutrophilic inflammatory response
    • Mucous plugging and atelectasis
    • Bronchiectasis and emphysema develop.
    • Abnormal nasal sinus development
  • In the gastrointestinal (GI) tract
    • Progressive pancreatic damage leads to exocrine pancreatic insufficiency.
    • Endocrine pancreatic dysfunction
    • Focal biliary cirrhosis of the liver
    • Hypoplasia of the gallbladder and impaired bile flow

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