CF and related

Question 1

classes of CFTR mutations

Answer 1

I = none
II = terribly misshapen so cant reach cell surface
III = gate activate PLEASE (not activated by ADP/cAMP)
IV = Cl falls through the floor = less Cl transported
V = fewer CFTR (splicing defect, reduced production)
VI = too quick (high turnover)

Question 2

most common mutation for CF

Answer 2

class II - deltaF508
present in 90% of australians

Question 3

severity of classically severe mutations most correlates with what?

Answer 3

degree of pancreatic insufficiency

Question 4

which class of mutations are severe?

Answer 4

I, II, III

Question 5

diagnostic criteria/process of CF

Answer 5

criteria:
1. phenotypic features OR CF sibling OR positve newborn test
PLUS
2. lab evidence of CFTR mutation (2 separate positive sweats, x2 CF mutations, abnormal nasal potential difference)

so:
1. phenotypic features OR CF sibling OR positve newborn test (IRT)
2. then get sweat test. >60 = CF. if intermediate:
3. get genetic testing. 2 mutations = CF. 1 mutation -> repeat sweat test.
if still uncertain -> CRMS/CFSPID

Question 6

how does the chloride test work?

Answer 6

CFTR helps chloride absorption in sweat (not excretion like in the other excretions)
pilocarpine on skin > chloride from sweat collected
>60 mEq/L diagnostic

Question 7

metabolic abnormality when CF get sick after hot day/exercising

Answer 7

excess Na/Cl loss from their sweat!
kidneys want to keep Na so they push H out&raquo_space;
hyponatraemic, hypochloraemic metabolic alkalosis

Question 8

what is an early functional change seen in PFT for CF

Answer 8

Decrease in the midmaximal flow rate – reflects small airway obstruction

Question 9

CF - obstructive or restrictive lung disease?

Answer 9

mostly obstructive
restrictive in very late disease and fibrosis

Question 10

what age will most CF kids show sign of bronchiectasis on CT?

Answer 10

90% by 5yo

Question 11

clinical manifestations of CF - all systems

Answer 11

sinuses - sinusitis, polyposis
pulmonary - recurrent infection, bronchiectasis, ABPA, haemoptysis
GI - pancreatic insufficiency, mec lieus, rectal prolapse, DIOS, pancreatitis, intussusception, biliary / liver fibrosis, adenocarcinoma
endo: CFRD, osteoporosis
renal/metabolic: hypoNa hypoCl met alkalosis, stones
other: infertility male

Question 12

what two factors are associated with slower lung decline?

Answer 12

males
exocrine pancreatic sufficiency

Question 13

DIOS - what age group

Answer 13

> 15yo

Question 14

what contributes to rectal prolapse in CF?

Answer 14

steatorrhoea, malnutrition and repetitive cough

Question 15

deficiencies in the four fat soluble vitamins will lead to what?

Answer 15

Vit E = neurological dysfunction and haemolytic anaemia
Vit K = hypothrombinaemia may lead to bleeding diathesis
Vit D = decreased bone density
Vit A = night blindness

Question 16

most common non-respiratory cx of CF

Answer 16

endocrine pancreatic dysfunction - CFRD

Question 17

CFRD usually occurs at what age?

Answer 17

2nd decade of life

Question 18

why is HbA1c less accurate in CF?

Answer 18

due to high cell turnover

Question 19

liver disease more likely in which CF patients?

Answer 19

mec ileus / panc insufficiency patients

Question 20

outline types of mucolytic therapy for CF

Answer 20

1) 6% hypertonic saline inhaled - draws water to mucous
2) mannitol - osmotic agent
3) pulmozyme/dornaze - DNase

Question 21

why give abx in first year of life?

Answer 21

staph prophylaxis with augmentin duo

Question 22

why azithromycin used in CF?

Answer 22

1. Suppresses alginate production
2. AZT increases lung function in patients with chronic pseudomonal patients
3. Widely used as immunosuppressive therapy to stabilise lung function

Question 23

name the CF modulator therapies, and what they are used for

Answer 23

Kalydeco® (ivacaftor) - G551D gating mutation >2yo
Orkambi® (lumacaftor/ivacaftor) - for 2 copies of deltaF508 >12yo
Symdeko® (tezacaftor/ivacaftor) - for those who cant take orkami
Trikafta® (elexacaftor/tezacaftor/ivacaftor) - heterozygous deltaF508

Question 24

biggest side effect of orkambi

Answer 24

chest tightness

Question 25

what is ABPA

Answer 25

ALLERGIC BRONCHOPULMONARY ASPERGILLOSUS = mixed immunological hypersensitivity reaction in the lungs and bronchi in response to exposure and colonization with Aspergillus species (usually Aspergillus fumigatus)

Question 26

three key features of ABPA

Answer 26

1. mucoid impaction of the bronchi
2. eosinophillic pneumonia
3. bronchocentric granulomatosis, classically central bronchiectasis

Question 27

two conditions ABPA is associated with

Answer 27

asthma
CF

Question 28

ABPA: features of CXR

Answer 28

UL infiltrates esp central

Question 29

Rx for ABPA

Answer 29

steroids
itraconazole
anti-IgE

Question 30

infections to know about and why in CF, and how to treat

Answer 30

• P aeruginosa = risk factor for pulmonary decline and reduced survival, more common in later adolescence. tobra, cpiro, aztreotam
• B cepacia = worse prognosis than P aeruginosa; CI to transplant
• Staphylococcus aureus = most common, aug duo or MRSA tx
• Haemophilus (non-typeable) = second most common early on, aug duo
• steno maltophilia = becoming more common, only treat if clinical deterioration (no LT effect), co trim
• NTM

Question 31

how many CF patients are affected with CFRD

Answer 31

20% young adults!

Question 32

PCD - key features

Answer 32

DIBS:
dextrocardia
infertility
bronchiectasis
sinusitis/MEE

Question 33

criteria for bronchiectasis diagnosis

Answer 33

i. Recurrent (>=3 episodes) wet or productive cough, each lasting >4 weeks, with or without other features
1. Exertional dyspnoea
2. Recurrent chest infections
3. Growth failure
4. Clubbing
5. Hyperinflation or chest wall deformity

ii. Presence of characteristic radiographic features on HRCT

Question 34

two most common causes of bronchiectasis in kids

Answer 34

CF
primary immunodeficiency

Question 35

gold standard Ix for bronchiectasis diagnosis

Answer 35

HRCT

Question 36

key features of different types of bronchiectasis on HRCT

Answer 36

1. Cylindrical = [tram lines, signet ring appearance]
2. Varicose = [beaded contour] degree of dilatation is greater with local constrictions
3. Saccular (cystic) = [strings and clusters], Most severe form

Question 37

compare the lobes affected in bronchiectasis vs ABPA bronchiectasis

Answer 37

bronchiectasis - more lower lobes
ABPA bronchiectasis - central bronch is classic

Question 38

pathogenesis of PCD - and most common abnormality

Answer 38

any abnormality of a ciliary structural protein (MOST COMMON is absence/shortening of dynein arms) > disordered orientation of cilia > can’t beat synchronously to clear mucous

Question 39

CF and PCD inheritance

Answer 39

AR

Question 40

what is the kartagner triad

Answer 40

infertility
chronic sinusitis/polyposis
situs invertus