Cystic Fibrosis

DISEASE STATE

Pathophysiology & Risk

Cystic Fibrosis (CF) is a genetic disorder 

  • Caused by an autosomal recessive mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
  • The mutation leads to errors in protein folding and trafficking, specifically affecting chloride-bicarbonate ion channels
  • Channel dysfunction ultimately leads to the production of thick and sticky mucus that can clog the airways and other organs
  • There are different genetic mutations among patients with Cystic Fibrosis, which can be categorized based on their clinical effects (see diagram to the right)

Common complications include:

  • Lung function and chronic infections
  • Pancreatic insufficiency and malnutrition
  • Infertility

Image from CFTR Modulators: Shedding Light on Precision Medicine for Cystic Fibrosis by Miquéias Lopes-Pacheco. Link: Frontiers | CFTR Modulators: Shedding Light on Precision Medicine for Cystic Fibrosis

Diagnosis

Newborn Genetic Screenings

  • Genetic screenings are commonly performed on newborns across the United States
  • The purpose is to increase early detection of certain disorders to improve morbidity and mortality
  • More common mutations, such as ΔF508, are widely included on these screenings
  • Less common mutations are frequently omitted from newborn testing - although, advocacy for expansion is ongoing

Sweat Chloride Testing

  • The "gold standard" for Cystic Fibrosis diagnosis
  • Non-invasive, sweat is collected through a special gauze or coil
  • The sweat is then tested for chloride content
    • Result Summary
      • < 30 mmol/L = CF unlikely
      • 30-59 mmol/L = Indeterminate
      • 60+ mmol/L = Consistent with CF

CF-Specific Genetic Testing

  • Further genetic testing can be done to detect a wider range of cystic fibrosis mutations
  • Some genetic mutations can be difficult to identify depending on their prevalence, it's possible to have patients with "unknown" mutations that present with clinical manifestations and have been diagnosed through a sweat chloride test

CHRONIC THERAPIES

Disclaimer: Agent choices and dosing can vary between institutions. If you are practicing or rotating at a specific institution, refer to your institution-specific pathways, order sets, and policies for available products, starting doses, titrations, and safety information. 

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators

SUMMARY: These drugs target the underlying defect in the CFTR protein. They can improve lung function, reduce exacerbations, and improve quality of life. Specific modulators are prescribed based on the individual's CFTR mutation.

Product Dosage Forms Qualifying Age Mutation
KALYDECO (ivacaftor) Tablet or Granules 4 months +
ORKAMBI (lumacaftor/ivacaftor) Tablet or Oral Granules Granules = 2-5 years; Tablets = 6 years+
SYMDEKO (tezacaftor/ivacaftor) Tablet 6 years +
TRIKAFTA (elexacaftor/tezacaftor/ivacaftor) Tablet 6 years +
ALYFTREK (vanzacaftor/tezacaftor/deutivacaftor) Tablet 6 years + Currently approved for 31 mutations (searchable on manufacturer website)

MECHANISM OF ACTION OF SUBCOMPONENTS

Potentiators: Ivacaftor, Deutivacaftor

Correctors: Lumacaftor, Tezacaftor, Elexacaftor, Vanzacaftor 

Airway Clearance Therapies

Pharmacologic

BRONCHODILATORS (e.g., Albuterol)

  • Relax airway muscles to improve airflow
  • Administered via nebulizer or inhaler

MUCOLYTICS (e.g., Dornase Alfa)

  • Break down DNA in mucus, making it less viscous
  • Administered via nebulizer

HYPERTONIC SALINE

  • Draws water into the airways, thinning mucus
  • Administered via nebulizer

Non-Pharmacologic

CHEST PHYSIOTHERAPY (CPT)

  • Mechanism: Manual techniques to help loosen and clear mucus from the airways.
  • Involves percussion, vibration, and postural drainage.

HIGH-FREQUENCY CHEST WALL OSCILLATION (HFCWO)

  • Uses an inflatable vest to deliver rapid chest compressions
  • Helps to loosen and thin mucus, making it easier to cough up

Inhaled Antibiotics

SUMMARY: Can be used for chronic suppression of lung infections (e.g., tobramycin, aztreonam). Administered via nebulizer.

Pancreatic Enzyme Replacement Therapy (PERT)

SUMMARY: Taken with meals to help digest fats and proteins. Dosage is adjusted based on individual needs and stool output.

Nutritional Supplementation

SUMMARY: Can be used for chronic suppression of lung infections (e.g., tobramycin, aztreonam). Administered via nebulizer.

Bowel Regimen

SUMMARY: Can be used for chronic suppression of lung infections (e.g., tobramycin, aztreonam). Administered via nebulizer.

Azithromycin

INFECTIONS & EXACERBATIONS

Information

 

ORAL ANTIBIOTICS

  • Used to treat acute lung infections.
  • Common choices include azithromycin, cephalexin, and others

 

INTRAVENOUS ANTIBIOTICS

  • Used for severe or refractory lung infections.
  • Administered in the hospital.

LITERATURE