Cystic Fibrosis

Question 1

What is Cystic fibrosis

Answer 1

A genetic autosomal recessive disease caused by defective ion transport.
- Imbalance of fluid and electrolytes causing thick, sticky mucus and viscous secretions to accumulate in different organ.(lungs, digestive systems)

Question 2

what is the Cystic fibrosis transmembrane regulator (CFTR)

Answer 2

it is a chloride channel that helps maintain salt, fluid and pH homeostasis

Question 3

State and ecplain the Class II and III CF gene mutation

Answer 3

Class II (F508del)
- The CFTR protein is made but cannot reach the cell surface (CFTR trafficking defect).
- The most common CF
- Caused by amino acid deletion and a protein processing mutation

Class III (Gly551Asp) :
- Defective channel gating:
- the protein teaches the surface but it does not do what its suppose to do because it is defected
- This type of gating mutation locks the gate in the closed position so that chloride cannot get through.
- Change in the amino acid

Question 4

Explain the diagnoses and symptoms of CF

Answer 4

Symptoms
- Fatigue
- chronic cough

DIAGNOSIS
Blood test
In new born babies will test for common gene alterations that cause CF

Sweat test  In child/adult, measure the amount of salt sweat   -  A painless electric current is applied to small area of skin with a harmless chemical. This was cause the area to sweat. A sample of sweat is collected and analysed.	- If salt content is abnormally high, then CF is confirmed.

Question 5

Why do people with CF have salty skin

Answer 5

because salts are not properly absorbed.

Question 6

Describe the pathophysiology of cystic fibrosis

Answer 6

CFTR defect
Defective ion transport
Airway surface liquid depletion
Defective mucoclliary clearance
Mucus obstruction
Infection
Inflammation

Question 7

Describe the classification of mucoactives

Answer 7

• expectorants
  induce cough or increase the volume of secretions
• mucolytics
  reduce the viscosity of mucus
• mucokinetic drugs
  increase the mobility and transportability of mucus
• mucoregulators
  control the process of hypersecretion

Question 8

Describe the CFTR treatment

i) mucoactives

ii) CFTR corrector and

iii) CFTR potentiator

Answer 8

TREATMENT

1. Mucoactives
Increases the ability to expectorate (cough or spit out)  sputum and or decreases mucus hypersecretion.


	a. Inhaled recombinant human DNase I -rhDNase 
	- Is a peptide mucolytic that degrades large amount of polymerised DNA and F-actin network that accumulates within CF mucus
	- Reduces viscosity of bronchial secretion. Improving the viscoelastic properties of airway secretions promotes airway clearance.
	
	b.  Hypertonic saline (7%)
	- Expectorant: draws water into the airways
	- Causes osmotic hydration of the periciliary layer and allows improved mucociliary clearance.
	
	c. Mannitol 
	- Osmotic agent: creates a luminal osmotic gradient, drawing water into the airway lumen. Other mechanism?
	- Improves hydration of airway secretions and reduces sputum viscosity to increase mucociliary clearance. Inhaled. 
	
2. CFTR Corrector

	a. Lumacaftor (only works for delta F508 patients)
	- Channel corrector acts as a protein folding chaperone, aids the conformational stability of the mutated CFTR protein. 
	- Thereby increases processing and trafficking of mature protein to the cell surface.
	- Specifically used in delta -F508 mutation
	
3. CFTR Potentiator
	a. Ivacaftor
	- Channel potentiator  by increasing the open-channel probability. Thus facilitates chloride transport
	- Specifically used in G551D mutations

Question 9

Describe the CFTR treatment

Answer 9

4. Chest physiotherapy
   Postural drainage and percussion:
   
   • Person gets in varied positions that help draining mucus
   • Chest is clapped and vibrated to help dislodge mucus to large airways.
     Note:
     · Use mucolytics and b- agonists before physiotherapy
   • Airway-oscillating devices, high-frequency chest wall oscillation devices
     
     • Person wears vibrating vest
   • Active Cycle of Breathing Technique
5. Immunomodulatory therapy
   
   • To provide immunoregulatory and anti-inflammatory effects.
     - Azithromycin (broad spectrum macrolide antibiotic)
     Long-term treatment at immunomodulatory dose for patient with CF and deteriorating lung function or repeated pulmonary exacerbation.
     250−500 mg 3 times weekly/ 6 months

Disadvantage: possible development of antibiotic resistance

6. Antimicrobials
   Flucloxacillin
   
   • Antibiotic prophylaxis
   • Use in children with CF from diagnosis up to age 3 (consider continuing up to 6 years of age!)

Question 10

Explain FOUR non-pharmacological treatment of CF

Answer 10

• Increase calorie intake
  
  • Increased portion size and eat high-caloric food
• Regular exercise
  
  • To improve both lung function and overall fitness.
• Consider oral nutritional supplements
  
  • Fat-soluble-vitamin supplementation.
• Pancreatic enzymes
  
  • To ensure proper digestion