Cystic fibrosis

Background

• Autosomal recessive genetic disorder
  • Mutation in cystic fibrosis transmembrane conductance regulator protein (CFTR) leads to defect of sodium/chloride exchange channel
  • Defect in chloride transport leads to thick, viscous secretions in lungs, pancreas, liver, intestines, reproductive tract
• Diagnosed by sweat chloride test
• Predicted life expectancy less than 40 years

Clinical Features

• Respiratory
  • Acute exacerbations lead to increase in baseline cough and sputum production
  • Pneumonia
    • Chronic colonisation with multiple organisms
    • Staph aureus and H. influenzae common in childhood
    • Most become chronically colonised with pseudomonas aeruginosa and/or virulent gram-negative bacteria
      • Colonisation with pseudomonas aeruginosa usually occurs by late adolescence
    • Pseudomonas features include: severe pneumonia, cyanosis, confusion, often bilateral, occasionally empyema
    • Higher risk for aspergillosis
  • Increased risk of pneumothorax (8%–20% will develop one in lifetime)
  • Bronchitis
  • Sinusitis and nasal polyps
  • Chronic inflammation and infection lead to bronchiectasis and angiogenesis (may have hemoptysis)
  • Long-standing disease can lead to cor pulmonale
• Gastrointestinal
  • Meconium ileus: failure to pass meconium within first 48 hours of life
    • Earliest clinical manifestation of disease
    • Occurs in 10 - 20% of those diagnosed
    • 90% of babies with meconium ileus have cystic fibrosis
    • Obstruction due to thick meconium
    • Can lead to perforation if unrecognized
    • Diagnosed and treated with hyperosmolar contrast enema
  • Pancreatic insufficiency
    • Often leads to failure to thrive in infancy
  • Pancreatitis
  • Diarrhea and malnutrition due to resultant malabsorption
• Other
  • Electrolyte disturbances
    • Chloride wasting and diarrhea can lead to hypokalemic, hypochloremic metabolic alkalosis
  • Suppurative parotitis
    • Rapid onset parotitis (warm, swollen, tender gland, fever, trismus)
    • Purulent drainage from Stensen's duct
    • Organisms: staph, strep pneumo, strep pyogenes, H. flu, e. coli, pseudomonas

Evaluation

• Sweat chloride test to make diagnosis, may also be diagnosed by amniocentesis if high suspicion antenatally (outside ED scope)
• CBC (signs of infection)
• Electrolytes
• LFTs and lipase (if concern for pancreatitis)
• Consider blood and sputum cultures (may have resistant organisms)
• CXR
  • Advanced disease: peribronchial thickening, mucous plugs, cystic/bullous lesions, atelectasis, hilar adenopathy, air trapping
  • Infiltrates if pneumonia
  • Pneumothorax

Short-Term Management

• Infections
  • Many patients already on maintenance azithromycin or tobramycin
  • Antibiotics for acute pneumonia must be broad and include pseudomonal coverage
    • e.g. Cefepime, Imipenem, OR Piperacillin/Tazobactam + IV fluoroquinolone, +/- vancomycin for MRSA
• Other respiratory adjuncts
  • Albuterol or other short-acting Beta-2 agonist
  • Dornase alfa (inhaled recombinant deoxyribonuclease I, hydrolizes DNA in sputum to decrease viscosity)
  • Nebulized hypertonic saline (reduce sputum viscosity)
  • Inhaled nitric oxide
  • Chest physical therapy
• See treatment for pancreatitis
• Rehydrate if volume depleted, replete electrolytes
• Note potential for hypoalbuminemia when giving extensively protein-bound drugs

Long-Term Management

• Chest physiotherapy
• Exercise therapy
• Pancreatic enzymes
• Fat-soluble vitamin supplementation
• Nebulised DNase
• Lung transplant

Disposition

• Dispo decision should be made in conjunction with patient's pulmonologist if possible, as they often know their patients very well

See Also

• Pneumonia
• Pseudomonas
• Diarrhea
• Metabolic alkalosis