Cystic Fibrosis

Question 1

What is Cystic Fibrosis?

Answer 1

An inheritable Autosomal Recessive disease caused by mutations of the Cystic Fibrosis Transmembrane conductase regulator Gene - CFTR.
It is when a chloride channel that has an importatnt role in the viscosity of mucous if affected. Ion transport abnormalities dehydrates the mucus, making it more thick and viscous.

Question 2

What is the epidemiology of CF?

Answer 2

70% of cases is due to a three-base pair deletion that should code for phenylalanine. There are thousands of other mutations. If a mutation occurs at any stage in the cellular processing of CFTR, the final protein and its function will be affected.
Prevelance varies with ethnicity: more prevelant in Caucasians (1 in 3000 live births)
Diagnosed in childhood
Median survival rate is to 30 years, but this is improving with better management.

Question 3

What are the other body systems affected by CF?

Answer 3

Sinuses, sweat glands, liver, pacreas, intestine, male reproductive system

Question 4

What is the correct cellular processing of CFTR?

Answer 4

1) Synthesis of the mRNA by transcription, then splicing
2) Translation and folding in the ER
3) Glycosylation and vesicle packaging in the Golgi body
4) Insertion and retrieval from the membrane
5) Activation by ATP binding and cAMP dependant phosphorylation
Mutation at any of these stages will result in cystic fibrosis.

Question 5

What is the sweat test?

Answer 5

This is not a definative diagnosis, but can be used to test the severity of CF:
-Very salty = severe
-Slightly salty = mild
This is a test of chlorine levels in the sweat. >60mM chlorine for adults indicates CF.

Question 6

What is the other test used to diagnose CF?

Answer 6

The Nasal transepithelial potential difference: the test would be more negative in CF patients due to increased luminal sodium absorption

Question 7

Why are DNA tests difficult to diagnose CF?

Answer 7

They are difficult because there are so many possible mutations of CF

Question 8

How is CF managed?

Answer 8

• A diverse team of medical proffesionals are required because of so many systems affected (not only the lungs)
• Life-style and physiological support
• Poly-pharmcay
• Maintenance to improve quality of life and limit exacerbations
• Treat exacerbations aggresively.

Question 9

What are the treatment objectives for treating CF?

Answer 9

Promote mucous clearance
Control lung infections
Provide adequate nutrients
Prevent intestinal obstruction

Question 10

Which infection has drug resistance?

Answer 10

P.aeruginosa

Question 11

What antibiotics are commonly used to treat infections due to CF?

Answer 11

Inhaled Tobramcyin

Inhaled Azithromycin

Question 12

Why do we use Tobramycin?

Answer 12

It treats chronic pulmonary infection. and is effective for all severities of CF.
It works by elevating and sustaining the FEV1, making it easier to breathe.
FEV1 = Forced Expiratory Volume in 1 second

Question 13

Why do we use inhaled Azithromycin?

Answer 13

Treats chronic pulmonary infection. Can only be used for up to 6 months to be safe and effective. Beond 6 months will still reduce exacerbations, but concerns over resistance. Its mechanism of action is unclear.

Question 14

What are the drugs used to promote mucous clearance?

Answer 14

Inhaled Dornase Alfa
Inhaled hypertonic Saline
Inhaled MAnitol

Question 15

Why do we use Inhaled Dornase Alfa?

Answer 15

A DNAse enzyme that breaks down DNA that form polymers so decreasign the thickness of the mucus

Question 16

Why do we use inhaled hypertonic saline?

Answer 16

THis disrupts the ionic bonds supporting the entanglements and dissassociates DNA from mucus proteins resulting in an improved access to endogenous proteolytics.

Question 17

Why do we use inhaled manitol?

Answer 17

Hydrates the mucous by an osmotic mechanism, making it less viscous

Question 18

What are the different ANti-inflammatories that could be used?

Answer 18

Oral corticosteroids
Inhaled corticosteroids
Ibuprofen

Question 19

Why use oral corticosteroids?

Answer 19

Prednisolone is not recommended due to the systemic side effects

Question 20

Why use inhaled corticosteroids?

Answer 20

Used only in a sub-set of asthma patients (not used unless they have asthma and CF)

Question 21

Why use Ibuprofen?

Answer 21

Reduce inflammation of the lung by targeting COX-2

Beneficial in young patients but not much evidenve in adults.

Question 22

What are the possible Bronchodilators that could be used? When are these used?

Answer 22

Inhaled SABA
Inhaled short-acting Muscarinic antagonists
Commonly used for acute relief of obatruction, Not much evidence

Question 23

what are the non-pharmacological interventions?

Answer 23

Chset physiotherapy to aid clearance of mucous from the lung

Question 24

What is the treatmetn of GI related disease of CF?

Answer 24

1) Take supplaments containing protease and lipase and amylase. Must be taken with food to prevent stomach acid from deactivating them.
2) High-calorie diet needed due to digestion being comprimised so they need more energy

Question 25

WHat are the future deveolpments in treating CF?

Answer 25

1) Modifiers of CFTR expression which is a mutation specific treatment. There are many drugs still in trial but The issue is that we need to know the mutation to know what treatment is necccessary.
2) Gene Therapy: Non-viral delivery of plasmid encoding CFTR gene. The issue is getting the package to the stem cell that produces the faulty gene. Still in trial and there is not much evidence that it will work.