Resp - Cystic fibrosis treatment

Question 1

What is CF?

Answer 1

genetic disorder affecting the lungs, pancreas, liver, intestine, and reproductive organs

Question 2

What are the signs of CF?

Answer 2

pulmonary disease, with recurrent infections and the production of copious viscous sputum, and malabsorption due to pancreatic insufficiency

Complications include hepatobiliary disease, osteoporosis, cystic fibrosis-related diabetes, and distal intestinal obstruction syndrome

Question 3

Aims of treatment

Answer 3

Preventing and managing lung infections

Loosening and removing thick, sticky mucus from the lungs

Preventing or treating intestinal obstruction

Providing sufficient nutrition and hydration

Question 4

What function is a key predictor?

Answer 4

lung function - optimising lung function is a major aim of care

Question 5

What are the Non-Drug Treatment?

Answer 5

Provide advice on airway clearance, nebuliser use, musculoskeletal disorders, physical activity, and urinary incontinence (by specialist physiotherapists).
Regular exercise improves both lung function and overall fitness

Question 6

What are the Drug Treatment?

Answer 6

Treatment is based on the prevention of lung infection and the maintenance of lung function.

Patients, who have clinical evidence of lung disease, the frequency of routine review should be based on their clinical condition.

Adults should be reviewed at least every 3 months.

More frequent review is required immediately after diagnosis

Question 7

Mucolytics

Answer 7

Patients with cystic fibrosis who have evidence of lung disease should be offered a mucolytic.
Dornase alfais the first choice mucolytic.
If there is an inadequate response,dornase alfaand hypertonicsodium chloride, or hypertonicsodium chloridealone should be considered.
Mannitoldry powder for inhalation is recommended as an option whendornase alfais unsuitable, when lung function is rapidly declining, and if other osmotic drugs are not considered appropriate

Question 8

Staphylococcus aureus

Answer 8

Offer an antibacterial oral or IV

Question 9

Pseudomonas aeruginosa

Answer 9

Offer an oral antibacterial in combination with an inhaled antibacterial

Question 10

Aspergillus fumigatuscomplex

Answer 10

Offer an antifungal drug only to suppresschroniccomplex respiratory infection in patients with declining pulmonary status

Question 11

Inheritable autosomal _________ disease

Answer 11

reccesive

Question 12

Mutations of the cystic fibrosis transmembrane conductance regulator ______ gene

Answer 12

CFTR

Question 13

Which systems are affected?

Answer 13

Pulmonary and GI systems

Question 14

Epidemiology of CF

Answer 14

equally diagnosed in males and females

Question 15

What is the most common mutation

Answer 15

ΔF508 - a three base-pair deletion that should code for a phenylalanine (position 508)

Question 16

What are the main causes

Answer 16

• CFTR gene, found at the q31.2 locus of chromosome 7, is 230,000 base pairs long, and creates a protein that is 1,480 amino acids long.
• CFTR gene, found at the q31.2 locus of chromosome 7, is 230,000 base pairs long, and creates a protein that is 1,480 amino acids long.

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Question 17

Cellular processing of CFTR:

Answer 17

1. Synthesis of mRNA (transcription)
2. translation and folding in the ER (splicing and folding)
3. Glycosylation and vesicle packaging in the Golgi
4. Insertion into and retrieval from membrane (stabilioty)
5. Activation by ATP binding and cAMP-dependent phosphorylation (activity and conductance)

Question 18

CFTR In Cystic Fibrosis

Answer 18

CFTR Channel: Chloride ions aren’t transported through chloride channels in CF
Chloride ions – reduced extraceullulary (on surface of epithelium)

Affects constituency of mucus

Na+ and Cl− on airway surfaces
coupled to reduced water flow to the airway lumen
dehydrating mucus
Reduced HCO3− to the airway surface, acidifying layer

Question 19

Diagnosis of CF

Answer 19

Large number of CFTR mutations limits utility of DNA tests in diagnosis but can be done
The heel prick test blood test newborns – common variants

Sweat test for chlorine levels (>60mM for adults)

Question 20

How to manage CF?

Answer 20

• Life-style and pyschological support required
• Maintenance to improve QoL and limit exacerbations

Question 21

Treatment objectives:

Answer 21

Promote clearance of secretions

Control lung infection

Provide adequate nutrition

Prevent intestinal obstruction

Question 22

What is the process of CF lung disease?

Answer 22

1. mutations of CFTR gene
2. ion transport abnormalities
3. overly viscous mucous
4. impaired mucous clearance (mucolytics)
5. infection (antibiotics)&raquo_space; inflammation which leads to tissue damage

Question 23

What happens in a pulmonary mucous clearance??

Answer 23

airway surface liquid protects lung and pericilary layer and mucus layer

the PCL is a grafted brush of tethered mucins

and mucus is a visocoelastic fluid

Question 24

What do ASL layers do?

Answer 24

trap and clear inhlaed pathogens from lung via mucociliary transport

mucus consistency affects this

ciliary clearence becomes ineffective

Question 25

Inhaled dornase alfa

Answer 25

DNA forms polymers thickening mucous
Dornase alfa is a DNAse
Reduces viscosity of mucous

Question 26

Inhaled hypertonic saline

Answer 26

Disrupts ionic bonds supporting entanglements
Disassociates DNA from mucous proteins
Improved access to endogenous proteolytics

Question 27

Inhaled mannitol

Answer 27

Hydrates mucous
Osmotic mechanism

Question 28

name examples of bronchodialators

Answer 28

Commonly used for acute relief of obstruction
No clinical studies on exacerbation

Question 29

Chest physiotherapy

Answer 29

Used to aid clearance of mucous from the lungs

Question 30

Oral corticosteroids

Answer 30

Reduce rate of decline in lung function
Reduce frequency of infections
Unwanted effects preclude long term use

Question 31

Inhaled corticosteroids

Answer 31

Don’t improve lung function unless airway hyperreactivity

Question 32

Pancreatic enzyme supplements

Answer 32

Supplements contain protease, lipase and amylase
Inactivated by stomach acid (with food, enteric coating)

Question 33

Why do you need a high calorie diet?

Answer 33

for digestion