Cystic fibrosis

From IDWiki
  • Autosomal recessive disease caused by missions in CFTR that causes a syndrome of respiratory disease, pancreatic insufficiency, constipation, and other disorders arising from the increased thickness of mucous production



  • Caused by mutations in the CFTR gene which encodes the cystic fibrosis transmembrane conductance regulator, a cAMP-regulated chloride channel
  • CFTR is present in epithelial cells lining the airways, biliary tree, intestines, vas deferens, sweat ducts, and pancreatic ducts >2000 possible defects, causing a wide range of presentations
  • Most common is delta-F508 (which falls into classes II, III, and VI)
  • Classified into:
    • Normal
    • I: no synthesis (e.g. a nonsense or frameshift mutation)
    • II: blocked processing or folding
    • III: blocked regulation or a gating problem
    • IV: altered conductance
    • V: reduced synthesis
    • VI: unstable and quickly degraded



  • Autosomal recessive disease
  • 1:3300 Caucasians
  • 1:25 carriers

Clinical Manifestations

  • On newborn screening, with increased serum trypsinogen (take top 2% and sequence for most common mutations)

Differential Diagnosis

  • For positive sweat chloride test:
    • Untreated Addison disease
    • Ectodermal dysplasia
    • Some glycogen storage diseases
    • Untreated hypothyroidism
    • Adulthood


  • Sweat chloride concentration greater than 60 mEq/L (or 90 mEq/L for adults) with an appropriate clinical context or family history
  • Genotyping


  • Must have both clinical features and positive diagnostic testing
  • Clinical features include cystic fibrosis, family history, or positive newborn screen
  • Diagnostic tests including 2x CF mutations, or 2x positive sweat chloride test


Chronic Management

  • Overall goals are to preserve lung function by decreasing infection, inflammation, and mucous production
  • Chronic *Pseudomonas *infection defined as >50% of cultures positive for Pseudomonas in the past 12 months
  • Vaccinations
  • Decrease mucous burden with mucolytics (hypertonic saline or Pulmozyme)
    • Chronic productive cough or FEV1 < 90%, start mucolytic
    • Mild lung disease, no daily cough, and FEV1 >90%, physician and patient decision
    • When starting, needs a trial of mucolytics with before-and-after PFTs to ensure no bronchospasm
  • Decrease bacterial burden with inhaled antibiotics (tobramycin, aztreonam)
    • Chronic growth of Pseudomonas, chronically suppress
    • New growth of Pseudomonas, attempt to eradicate with short course
    • B. cepacia complex, physician decision
    • Stenotrophomonas maltophilia, physician decision
    • Achromobacter xyloxidans, physician decision
  • Decrease inflammation with chronic oral azithromycin
    • Chronic growth of Pseudomonas, treat if no Mycobacteria
    • B. cepacia complex, no guidelines
    • Staph aureus, H. influenzae, physician decision (small benefit)
    • Rule out non-tuberculous mycobacteria first
  • Targeted therapies
    • For G551D (3% of cases) (a class III defect in gating), ivacaftor (VX700) is an experimental agent that causes an absolute increase in FEV1 by 10%

Acute Management


  • FEV1 is main predictor of survival
  • FEV1 starts declining after Pseudomonas colonization
  • Survival decreases with increasing pulmonary exacerbations
    • 25% fail to recover to 90% of baseline FEV1
    • 40% fail to recover to 100% of baseline FEV1
  • Life expectancy is 1 year once FEV1 drops to 20% of predicted