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Flashcards in Cystic fibrosis Deck (18):
1

What is cystic fibrosis?

Inheritable autosomal recessive disease
Mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene
Ion transport abnormalities dehydrates mucous becoming more viscous
Pulmonary and GI systems principally affected

2

Epidemiology

Must common mutation is a three base-pair deletion that should code for a phenylalanine
Usually diagnosed in childhood, median survival is around 30 years
Prognosis is improving

3

Body systems affected by CF

Lungs and sinuses
Sweat gland
Liver
Pancreas
Intestine
Male reproductive tract
Airway obstruction

4

Cellular processing of CFTR

Activation by ATP binding and cAMP-dependent phosphorylation
Insertion into and retrieval from membrane
Glycosylation and vesicle packaging in the golgi
Translation and folding in the ER
Synthesis of mRNA

5

Diagnosis of CF

Large number of CFTR mutations limits utility of DNA tests in diagnosis
Sweat test for chlorine levels (>60mM for adults)
Nasal transepithelial potential difference (same lining as lining of the lungs)

6

Management of CF

Lifestyle and psychological support required
Poly-pharmacy is required
Maintenance to improve QoL and limit exacerbations
Treat exacerbations aggressively

7

Treatment objectives

Promote clearance of secretions
Control lung infection
Provide adequate nutrition
Prevent intestinal obstruction

8

Antibiotics: Tobramycin

Inhaled
Treats chronic pulmonary infection
Effective for all severities of CF

9

Antibiotics: Macrolides

Inhaled
Treats chronic pulmonary infection
Use for up to 6 months safe and effective
Beyond 6 months can reduce exacerbations but concern over resistance
Mechanism of action unclear

10

Pulmonary mucous clearance

Can't move mucous as too thick for cilia
Enzymes/ immunity cells to kill bacteria cannot cross mucous so bacteria are free to grow

11

Promoting mucous clearance: inhaled dornase alfa

DNA forma polymers thickening mucous, dornase alfa is a DNAse, reduces viscosity of mucous

12

Promoting mucous clearance: inhaled hypertonic saline

Disrupts ionic bonds supporting entanglements, disassociates DNA from mucous proteins, improved access to endogenous proteolytics

13

Promoting mucous clearance: inhaled mannitol

Hydrates mucous by pulling fluid from underlying tissue, osmotic mechanism

14

Anti-inflammatories

Oral corticosteroids: not recommended, too many side effects
Inhaled corticosteroids: used in sub-set with asthma patients
Ibuprofen: reduce lung inflammation, little evidence of benefit in adults, beneficial in young patients

15

Bronchodilators

Inhaled bronchodilators (salbutamol, ipratropium): commonly only used for acute relief of obstruction, no clinical studies on exacerbation

16

Non-medical interventions

Chest physiotherapy: used to aid clearance of mucous from the lungs

17

CF GI disease

Pancreatic enzyme supplements: contain protease, lipase and amylase, inactivated by stomach acid (take with food, enteric coating)
Diet: high calorie diet needed as digestion compromised

18

Future developments

Modifiers of CFTR expression (mutation specific)
Gene therapy: non-viral delivery of plasmid encoding CFTR gene, phase 2b trial complete, only modest clinical outcome, proof gene therapy might work