3 - Cystic Fibrosis

cystic fibrosis (CF)

autosomal recessive genetic disorder that causes thick mucus that is hard to expectorate

cystic fibrosis transmembrane conductance regulator (CFTR)

protein that regulates Na⁺ and Cl⁻ in and out of cells

steps of CFTR mutation

1. Cl⁻ trapped in cell

2. H₂O not attracted to extracellular space

3. mucus loses H₂O and thickens

4. cilia are unable to move mucus

5. frequent lung infections, destroyed pancreas, and other organ complications

prognosis of CF

significant morbidity, premature mortality

• median life expectancy 46.2 years

diagnosis for CF

• clinical features

• family history

• immunoreactive trypsinogen test

• sweat chloride test

• mutation analysis

criteria for CF

phenotypic

• persistent infection with CF pathogens

• chronic productive cough

• CXR abnormalities (bronchiectasis, hyperinflation, etc.)

• PFT obstruction patterns

• nasal polyps and chronic sinus involvement

• digital clubbing

• GI abnormalities

• acute salt depletion

• males: obstructive azoospermia caused by obstructed vas deferens

genotypic

• > 60 mmol/L Cl⁻ on sweat test with no other cause

• 2 mutant CFTR genes

sweat chloride test

CF test that induces sweating to check for Cl⁻ levels

• positive: > 60 mmol/L on 2+ occasions (> 40 mmol/L for infants)

respiratory manifestations for CF

• dyspnea

• productive cough

• thick sputum

• digital clubbing

• frequent lung infection

• chronic sinus infection

• fatigue

• anorexia

• weight loss

• hyperinflation

• bronchiectasis

common CF bacteria

• Pseudomonas aeruginosa

• Staphylococcus aureus

extrapulmonary manifestations of CF

upper respiratory tract

• opacification of paranasal sinuses

• nasal obstruction of chronic sinusitis

pancreas

• exocrine pancreatic insufficiency (fat, sometimes protein)

GI

• meconium ileus

liver

• focal biliary cirrhosis

male reproductive

• 98% infertility

sweat

• increased Cl⁻

respiratory complications of CF

• hemoptysis

• pneumothorax due to subpleural air cysts

• respiratory failure

  • late stage: ↓O₂, ↑CO₂

  • causes 80% of deaths

  • may need lung transplant

maintenance therapy for CF

• airway clearance techniques

• bronchodilators

• dornase alfa (Pulmozyme)

• hypertonic saline

• mannitol

• antibiotics

  • tobramycin

  • cayston

• anti-inflammatory meds

  • oral corticosteroids

  • ibuprofen

• infection prevention

airway clearance techniques

• CPT

• active cycle of breathing technique (ACBT)

• autogenic drainage (AD)

• PEP

• oscillatory PEP (OPEP)

• high-frequency chest wall compression (HFCWC)

Trikafta®

new treatment for CF approved in 2019

• for patients 6+ years old with certain CFTR mutations

• fixes CFTR protein

• benefits

  • improved lung function

  • decreased sweat chloride

  • fewer exacerbations

  • increased BMI

• NOT A CURE!