CF and related Flashcards
classes of CFTR mutations
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)
most common mutation for CF
class II - deltaF508
present in 90% of australians
severity of classically severe mutations most correlates with what?
degree of pancreatic insufficiency
which class of mutations are severe?
I, II, III
diagnostic criteria/process of CF
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
how does the chloride test work?
CFTR helps chloride absorption in sweat (not excretion like in the other excretions)
pilocarpine on skin > chloride from sweat collected
>60 mEq/L diagnostic
metabolic abnormality when CF get sick after hot day/exercising
excess Na/Cl loss from their sweat!
kidneys want to keep Na so they push H out»_space;
hyponatraemic, hypochloraemic metabolic alkalosis
what is an early functional change seen in PFT for CF
Decrease in the midmaximal flow rate – reflects small airway obstruction
CF - obstructive or restrictive lung disease?
mostly obstructive
restrictive in very late disease and fibrosis
what age will most CF kids show sign of bronchiectasis on CT?
90% by 5yo
clinical manifestations of CF - all systems
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
what two factors are associated with slower lung decline?
males
exocrine pancreatic sufficiency
DIOS - what age group
> 15yo
what contributes to rectal prolapse in CF?
steatorrhoea, malnutrition and repetitive cough
deficiencies in the four fat soluble vitamins will lead to what?
Vit E = neurological dysfunction and haemolytic anaemia
Vit K = hypothrombinaemia may lead to bleeding diathesis
Vit D = decreased bone density
Vit A = night blindness
most common non-respiratory cx of CF
endocrine pancreatic dysfunction - CFRD
CFRD usually occurs at what age?
2nd decade of life
why is HbA1c less accurate in CF?
due to high cell turnover
liver disease more likely in which CF patients?
mec ileus / panc insufficiency patients
outline types of mucolytic therapy for CF
1) 6% hypertonic saline inhaled - draws water to mucous
2) mannitol - osmotic agent
3) pulmozyme/dornaze - DNase
why give abx in first year of life?
staph prophylaxis with augmentin duo
why azithromycin used in CF?
- Suppresses alginate production
- AZT increases lung function in patients with chronic pseudomonal patients
- Widely used as immunosuppressive therapy to stabilise lung function
name the CF modulator therapies, and what they are used for
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
biggest side effect of orkambi
chest tightness
what is ABPA
ALLERGIC BRONCHOPULMONARY ASPERGILLOSUS = mixed immunological hypersensitivity reaction in the lungs and bronchi in response to exposure and colonization with Aspergillus species (usually Aspergillus fumigatus)
three key features of ABPA
- mucoid impaction of the bronchi
- eosinophillic pneumonia
- bronchocentric granulomatosis, classically central bronchiectasis
two conditions ABPA is associated with
asthma
CF
ABPA: features of CXR
UL infiltrates esp central
Rx for ABPA
steroids
itraconazole
anti-IgE
infections to know about and why in CF, and how to treat
• 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
how many CF patients are affected with CFRD
20% young adults!
PCD - key features
DIBS:
dextrocardia
infertility
bronchiectasis
sinusitis/MEE
criteria for bronchiectasis diagnosis
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
two most common causes of bronchiectasis in kids
CF
primary immunodeficiency
gold standard Ix for bronchiectasis diagnosis
HRCT
key features of different types of bronchiectasis on HRCT
- Cylindrical = [tram lines, signet ring appearance]
- Varicose = [beaded contour] degree of dilatation is greater with local constrictions
- Saccular (cystic) = [strings and clusters], Most severe form
compare the lobes affected in bronchiectasis vs ABPA bronchiectasis
bronchiectasis - more lower lobes
ABPA bronchiectasis - central bronch is classic
pathogenesis of PCD - and most common abnormality
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
CF and PCD inheritance
AR
what is the kartagner triad
infertility
chronic sinusitis/polyposis
situs invertus
