Cystic fibrosis medical therapy

Medical treatments for patients with cystic fibrosis has targeted following consequences of the defect such as GI and pulmonary mucus plugging and infection. Treatment include mucolytic agents (dornase alfa, N-acetyl-L-cysteine), airway surface rehydration (hypertonic saline, osmotic agents), anti-infective agents (for prophylaxis, eradication of early infection and suppression of chronic infection), anti-inflammatory agents (NSAIDs, inhaled corticosteroids, LTB4 receptor antagonists and Azithromycin) and potentiators of CFTR protein defect.

• Treatment for cystic fibrosis has targeted following consequences of the defect such as GI and pulmonary mucus plugging and infection.
• Medical treatments for patients with cystic fibrosis are include:^[1][2][3]

• 1 Mucolytics
  • 1.1 Recombinant human deoxyribonuclease I (rhDNase) enzyme
    • Preferred regimen (1): Dornase alfa

    Note (1): Cleave the extracellular DNA and aid airway clearance.

  • 1.2 Clevage of disulfide bonds in the mucoproteins
    • Preferred regimen (1): N-acetyl-L-cysteine

    Note (1): Also increase levels of the intracellular antioxidant glutathione (GSH) that protect against the neutrophil-driven tissue damage.

• 2 Airway surface rehydration

  • Preferred regimen (1): Hypertonic saline

  Note (1): As it may cause bronchoconstriction, it is commonly used with an bronchodilator.

  • Preferred regimen (2): Osmotic agents

  Note (2): Mannitol is a nonabsorbable sugar alcohol which provides an osmotic gradient on the airway surface

  • Preferred regimen (3): Correction of ion transport

• 3 Anti-Inflammatory agents

  • Preferred regimen (1): Nonsteroidal anti-inflammatory agents (NSAIDs)

  Note (1): Ibuprofen showed some benefit in young patients with mild disease in high doses.

  • Preferred regimen (2): Inhaled corticosteroids
  • Preferred regimen (3): LTB4 receptor antagonists

  Note (2): Leukotriene B4 (LTB4) is produced by macrophages and PMNs in response to infection and plays a significant role in inflammatory response.

  • Preferred regimen (4): Azithromycin

• 4 Anti-infective agents
  • 1.1 Prophylaxis
    • Preferred regimen (1): Flucloxacillin

    Note (1): Anti-staphylococcal antibiotics (such as flucloxacillin) until ~3 years of age is recommended to reduce the incidence of methicillin-susceptible S. aureus (MSSA)

  • 1.2 Eradication of early infection
    • Preferred regimen (1): Tobramycin

    Note (1): If P. aeruginosa not detected and treated aggressively, this gram-negative, opportunistic bacterium will become chronic.

  • 1.3 Suppression of chronic infection
    • Preferred regimen (1): Tobramycin
    • Preferred regimen (2): Colistin
    • Preferred regimen (3): Aztreonam
  • 1.4 Acute exacerbations

    Note (1): Pulmonary exacerbations are treated with oral or IV antibiotics depending on severity.

• 5 CFTR protein defect
  • 1.1 Potentiators
    • Preferred regimen (1): Ivacaftor

    Note (1): Enhance the activity of the CFTR channel if it is correctly located.

    Note (2): The most significant advance in the treatment of CF over the last few years has been the development of Ivacaftor (Ivacaftor increases the time the CFTR channel is open)

  • 1.2 Correctors and combination therapy
    • Preferred regimen (1): lumicaftor/ivacaftor