Cystic Fibrosis

Usually diagnosed in childhood
Carrier rate: 4-5% of Caucasian population
U.S. Prevalence (2024): 40,000
Incidence in live births
1. Caucasian: 1:1500 to 1:2000 (up to 91% of U.S. CF patients)
2. Hispanic: 1:9000 (up to 10% of U.S. CF patients)
3. Black: 1:17000
4. Asian: 1:90000

Autosomal Recessive trait (Chromosome 7)
1. Mutation in CF transmembrane conductance regulator (cftr) Protein
2. Cftr mutations are grouped into 5 classes, with more than 2000 known mutations
3. Cftr Protein is a chloride channel on apical membrane of cells (regulates chloride and other molecule flow)
Cftr Protein is present on multiple cell types
1. Exocrine gland disorder produces mucus blockage
2. Blocks fine tubules in various organs (respiratory, gastrointestinal, endocrine, Pancreas, reproductive)

Positive CF Newborn Screening
1. Universal CF screening in U.S. since 2010
2. Mild CF or rare mutations may be missed of standard screening (esp. in minority groups)
  1. Missed CF with delayed diagnosis is associated with poor outcomes
Other presentations
1. Poor weight gain, Failure to Thrive or Malnutrition
2. Growth Delay
3. Digital Clubbing
4. Chronic respiratory symptoms
  1. Cough, Wheezing or Shortness of Breath
  2. Recurrent respiratory or sinus infections
  3. Nasal Polyposis in children
5. Chronic gastrointestinal symptoms
  1. Steatorrhea or frequent bulky stools

Newborn Screening positive for 2 CF mutations
1. Contact local Cystic Fibrosis center
2. Discuss with family and perform evaluation
3. Obtain confirmatory diagnostic Sweat Test
Newborn Screening positive for 1 CF mutation
1. Alternatives: Ultra-high immunoreactive trypsinogen or other presentation as above
2. Obtain Sweat Chloride test at CFF accredited lab
  1. Sweat Chloride >= 60 mmol/L: Consistent with Cystic Fibrosis (refer as if 2 CF mutations)
  2. Sweat Chloride <= 29 mmol/L: Cystic Fibrosis is unlikely
  3. Sweat Chloride 30 to 59 mmol/L: Intermediate for CF
    1. Consult with local CF center
    2. Consider repeat Sweat Chloride, Genetic Testing or evaluation at CF center

See Cystic Fibrosis in Pregnancy
Cystic Fibrosis Care Center visits every 3 months
Ongoing monitoring
1. Annual labs including Liver Function Tests, Glucose (e.g. OGTT, Hemoglobin A1C)
2. Following care plan (e.g. airway management, supplements, CFTR Modulators)
3. Annual Vaccinations (e.g. Influenza Vaccine, covid19 Vaccine) as well as Pneumococcal Vaccine
4. General preventive care and screening (mental health, substance use including Alcohol Use Disorder)

Mechanism
1. CF disease modifying agents
2. Partially returns function of chloride channels, resulting in less mucus accumulation
Preparations
1. Trikafta (elexacaftor/tezacaftor/ivacaftor)
  1. Released in 2020, targets gene mutation found in 90% of CF patients (contrast with 50% for other agents)
2. Kalydeco
3. Orkambi
4. Symdeko
Dosing
1. To maximize absorption, take with fat containing food such as peanut butter or avocado
2. Also take with Pancreatic Enzymes (if already taking)
Adverse Effects
1. Expensive ($300,000 per year)
2. Liver Function Test Abnormalities
Drug Interactions
1. Strong CYP3A4 Inducers
2. Moderate to Strong CYP3A4 Inhibitors
References
1. (2020) presc lett 27(2):11

Airway clearance
1. Percussion and postural drainage
2. Active cycle breathing
3. Positive expiratory pressure mask
4. Autogenic drainage
5. Flutter valve
6. Pneumatic vest
Mucus thinning drugs
1. Pulmozyme 2.5 mg nebulized qd
2. Efficacy maintained for up to 1 year of treatment
3. Reduces rate of respiratory infection
4. Improves pulmonary function
Antibiotics: Nebulized Tobramycin
1. Traditional Tobramycin
  1. Dose: 80 mg/2cc nebulized TID
2. TOBI
  1. Dose: 300 mg/5cc nebulized bid via Pari LC Plus
  2. Cost: $2000/28 day supply
Antibiotics: Pneumonia
1. Under age 10 years: Multiple organisms
2. Age 10 and older: Pseudomonas predominates

Background
1. Nutritional status impacts longterm survival and pulmonary function
Targets
1. Dietary plan maintains 90% of Ideal Body Weight (or BMI 22 to 25 kg/m2)
Labs
1. Monitor pancreatic exoocrine function (with fecal pancreatic elastase)
Supplements as needed
1. Daytime
  1. Scandibar 350 cals/bar
  2. Scandishake 600 cals/8 oz (with WCM)
  3. Calories Plus 450 cals/8 oz (with water)
  4. Carnation Instant Breakfast 290 Cals/8 oz
2. Nighttime drip (e.g. Gastrostomy Tube)
  1. Tolerex 1.0 cal/cc
  2. Vital 1.0 cal/cc
  3. Peptamen 1.0 cal/cc
  4. Criticare 1.0 cal/cc
Other gastrointestinal symptoms
1. Gastroesophageal Reflux management
  1. Proton Pump Inhibitors or H2 Blockers
2. Constipation (common)
  1. See Chronic Constipation

Mean survival has significantly improved from age 36 years (2006) to age 53 years (2021)