Cystic Fibrosis

Front 1

What are the important ions?

Back 1

Bicarbonate, chloride

Front 2

Why is dehydrated airways a problem?

Back 2

Thick mucus

Cilla can't beat, because they can't stand up

Exposure to epthililal cells, which cause a cytokine/immune response.

The low volume hypothesis

Front 3

What is the most common mutation?

Back 3

Class 2. DeltaF508

Front 4

Symptoms and consequences

Back 4

still need to complete

Front 5

What is Bronchiectasis?

Back 5

It is a dilation of the airway, and thickening of the wall

Front 6

What does ImpairedCl- secretion; Increased Na+/H2O absorbtion & Impaired MCC lead to?

Back 6

Thick,dehydrated mucus

Bacterialinfection & XS inflammation

Front 7

CF is a ____ disease

Back 7

spectrum

Front 8

CBAVD

Back 8

Congenital absence of the vas deferens

Front 9

Function of bicarbonate ions?

Back 9

google that

Front 10

Diagnosis means

Back 10

–Newborn screening–Sweattesting–Otherdiagnostic tests

Front 11

Newborn screening

Back 11

Checks for high Immunoreactive trypsinogen

Front 12

Advantages of early diagnosis

Back 12

•Betternutrition, because they can't normally digest food due to lack of pancreatic enzymes

• Earlyphysio,antibiotics etc

• Lessevidence for lung function

• Geneticcounselling/ pre-natal diagnosis for parents

Front 13

Potentialdisadvantages

Back 13

–Missedcases, rare genotypes

–Falsepositives

–Lossof awareness of clinical presentation

Front 14

Sweat testing

Back 14

Test for ions, most common for chlorine.

Front 15

What stimulates sweat test?

Back 15

pilocarpine. The sweat test measures the concentration of chloride that is excreted in sweat. It is used to screen for cystic fibrosis (CF).[ Due to defective chloride channels (CFTR), the concentration of chloride in sweat is elevated in individuals with C

Front 16

How do weMaintainpulmonary health:

Back 16

–Asymptomatic

–Freefrom infection:

•Eradicateearly

•Nochronic infection

–Noinflammation

–Freefrom ‘respiratory exacerbations’

–Normallung function

Front 17

What are we trying to achievewith modern CF management?

Back 17

•Normalgrowth, nutrition and development•Freefrom complications

Front 18

What Respiratory problems as infants?

Back 18

– Cough

– Wheeze

– Pneumonia

– ‘bronchiolitis’

– Recurrentinfections

Front 19

What Respiratory problems when older?

Back 19

•Older:

–Sputumproduction

–Nasalpolyps/ sinusitis

–Fingerclubbing

Front 20

How do we assess respiratorydisease?

Back 20

•Physicalexamination

•Microbiology

•Radiology:–CXR,CT (rare), ventilation scan•Physiology:

–Spirometry/(plethysmography)

–Oximetry

–Noveltests: lung clearance index

•Bronchoscopy

Front 21

How to distinguish asthma from CF?

Back 21

finger clubbing is only in CF

Front 22

What is the most common bacteria for CF?

Back 22

P. Aeruginosa

Front 23

The role of bronchoscopy

Back 23

clears mucus, and also spotting infects

Front 24

Respiratory treatment

Back 24

• Airwayclearance:

• Antibiotics:

• Anti-inflammatory

• Anti-fungal/allergic (ABPA)

• Transplantation

Front 25

Indwelling intravenous accessdevices

Back 25

gives antibiotic intravenously

Front 26

Gastrointestinal problems

Back 26

•Exocrinepancreas

•Meconiumileus:

•MIE

•Rectalprolapse

•Liverdisease

Front 27

Class 1

Back 27

STOP codon causes no synthesis

Front 28

Class 2

Back 28

Block inprocessing DF508

Front 29

Class 3

Back 29

Block inregulation

Front 30

Class 4

Back 30

Alteredconductance

Front 31

Class 5

Back 31

Reducedsynthesis

Front 32

Class 6

Back 32

Reducedretention, the turn over of the receptor is too quick. Not enough of them

Front 33

Which are severe for pancreas disease?

Back 33

I, II, III = severe mutation

Front 34

Which are mild for pancreas disease?

Back 34

IV, V, VI =mild mutation

Front 35

What influences the disease severity?

Back 35

CFTR mutation

Environment

Social-economic factors

Front 36

Putative Modifiers?

Back 36

HOST DEFENCE

ION CHANNELS

AIRWAY FUNCTION

CFTR FUNCTION

Front 37

CF Lung Disease: Principles of Treatment

Back 37

•Airway clearance (physiotherapy,DNase)

DNase breaks down DNA. Makes sputum more liquid.

Front 38

CF Lung Disease: Principles of Treatment

Back 38

• Reduction of inflammation (anti-inflam drugs)

– Bronchodilators

• Control and treatment of infection (antibiotics)

Front 39

Why is gene therapy hard?

Back 39

Cilla, mucus, prevents the absorption of genes into the small bronchioles

Viral vectors cause immune reactions

Front 40

Why is a sheep muscle than a mouse?

Back 40

Live longer, more like humans,

Front 41

DNA/LiposomeComplexes advantage?

Back 41

no immune reaction. Can give multiple times

Front 42

Correction-how much do we need?

Back 42

only 10%, because there is a non linear correlation between CFTR and clinical severity. People can be alright with just 10%

Front 43

Best gene transfer agent?

Back 43

lipid formulation with an improved plasmids.

CpG-depleted, Codon-optimised, Long-lasting promoter(hCEFI)

Front 44

What is the dilemma when choosing the age of CF patients?

Back 44

young patients which have less mucus, hence better delivery. But the lack of disease means measuring is quite hard.

Front 45

What is F/HN-pseudotyped Lentivirus?

Back 45

Its a sendal virus and lentivirus.

A sendal virus: lso known as murine parainfluenza virus type 1 or hemagglutinating virus of Japan (HVJ), is a negative sense, single-stranded RNA virus of the family Paramyxoviridae,

Front 46

CF can be corrected withCFTR Modulators

Back 46

PotentiatorsVX770, opens Cl channels in type 3 mutations

Front 47

VX-809

Back 47

The drug is designed to be effective in patients that have the F508del mutation in the cystic fibrosis transmembrane conductance regulator

Front 48

Osmotic therapy helps?

Back 48

airways surface liquid depletion and helps clearing mucus