- Progressive pulmonary and pancreatic insufficiency.
- A disease of western lineage – 1/25 europeans carry gene. Seen equally in M/F. If both parents carry – risk is ¼ (homozygous recessive).
- UK incidence: 1/2500, Asia: 1/90,000!
- Multisystem disease
- Chronic lung infections include: Staphylococcus aureus and Hemophilus influenzae colonize and infect the lungs. Eventually, Pseudomonas aeruginosa (and sometimes Burkholderia cepacia) dominates
*Atelectasis: lack of GE in alveoli due to collapse/fluid/consolidation
*Bronchiectasis: dilated bronchioles caused by congenital (CF/PKD), immunodeficiency and repeated infections, or acquired (trauma, foreign body, allergic bronchopulmonary aspergillosis [ABPA]). p/c: purulent sputum, haemoptysis, CP, wt loss, COPD. MAIN CAUSE = CF!
- Sweat test (gold standard): >60mmol = +ve test, 40-60 = equivocal, <40 = -ve test. If +ve sweat test and >2 features = diagnosis complete.
- Screening/genetic testing: blood DNS analysis.
- Newborn screening for immunoreactive trypsinogen (IRT on Guthrie Card)
- Faecal elastase: if pancreas blocked = reduced FE and therefore increased faecal fat. In normal health = normal FE, low faecal fat.
- CXR = bronchiectasis
- CT, DEXA…
- Genetic – chromosome 7 (7q31). Mutation delta F508 = mutated CF transmembrane conductance regulator (CFTR = type of GPCR). Frequency = 66-70% of cases.
- Second most common mutation: G542X (2.4%)
- ΔF508, for instance, creates a protein that does not fold normally (abnormal CFTR) and is degraded by the cell.
- The transmembrane protein created by this gene is anchored to the outer membrane of cells in the sweat glands, lungs, pancreas, and other affected organs.
- In the sweat ducts it facilitates the movement of chloride from the sweat into the cytoplasm. When the CFTR protein does not work, it is destroyed and chloride is trapped inside the cells in the airway and outside in the skin. Sodium is the most common ion in the extracellular space and the combination of sodium and chloride creates the salt, which is lost in high amounts in the sweat of individuals with CF – This lost salt forms the basis for the sweat test.
- How this malfunction of cells in cystic fibrosis causes the clinical manifestations is not well understood.
- Hereditary – autosomal recessive pattern of inheritance (2 carriers = ¼ disease, ¼ not, ½ carrier)
Treatment and management (conservative/medical/surgical)
- Airway infection management – prophylactic IV or aerosolised Abx (vancomycin/ciprofloxacin)
- Dornase-alfa and carbocysteine can help loosen mucus (mucolytics)
- Healthy lifestyle and good nutrition (may require Creon supplementation) to support GI health
- Vigorous percussive chest physiotherapy to loosen and expel mucus secretions
- Organ transplantation (mainly lung)
- Mechanical ventilation
- Gene therapy: deliver health CFTR using adenovirus vectors
Life expectancy between 20-40. Ever increasing with new technologies and health care.