Cystic Fibrosis and Bronchiectasis: Clinical Correlation

Question 1

CF genetics

Answer 1

Auto recessive

CFTR mutation

IN US, DeltaF508

85% carry at least one copy and 50% homo

CFTR - membrane associated chloride channel and you get defective ion transport across and within epithelial cells

Question 2

CFTR classes

Answer 2

Severe - pancreatic insufficiency and decreased sufficiency

Mild - pancreatic sufficiency

1 - stop codon
2 - doesn’t fold right and can’t get in golgi
3 - chloride channe lthere but it won’t open
4- works but the defect is in the pore
5- transcription…not enough of it

Question 3

Upper airways 
Lungs 
Panc
Liver
Intest
Resprodutive 

CF

Answer 3

Chronic sinusitis

Recurrent infection, bronchiect

Pancreatic insuff, diabetes

Cirrhosies

Meconium ileus, distal intestinal obstruction

Infertility

Question 4

Gold std dx

Answer 4

Sweat test

Chloride concentration is measured…higher is more indicative of CF (over 60)

Question 5

Dx

Answer 5

One of these - over 1 typical phenotypic feautre, sibling, pos newborn screen

PLUS - elevated sweat, 2 ID’d CFTR genes, abnormal nasal potential diff test

Question 6

Mucous clearance from the lung depends on

Answer 6

Hydrated airway surface fluid

Question 7

Patho

Answer 7

Defective gnee

Def CFTR

Decreased chloride secretion and increased sodium absorption

Bornchial obnstruction

Infection

Inflammation

Bronchiectaiss

Question 8

Broncheictasis

Answer 8

Acqwuired dz of major bronchi and bronchioles with permanent dilitation and destruction of bronchial walls

SUaully wit hchornic bac infection

Question 9

Patho of bronchiect

Answer 9

Infection PLUS

Impaired mucociliary clearance, airway obstruction, or a defect in host defense

Question 10

Bronch sx and signs

Answer 10

Cough, sputum, hemoptysis

Signs - crackles, wheezing/rhonchi, clubbing

Question 11

Tx infeciton in CF

Answer 11

IV Abs to tx pseudomonas

Oral anti-psuedomonas ABs - approval of fluroquinos in children

INhaled ABs

Infection control practices

Surveillance of resp cultures

Pseudo erad protocols

Chronic suppression therapy

Question 12

Tx inflammation

Answer 12

Oral CSs

Inhaled CSs

Azithromycin and ibuprofen (chronically)

Question 13

Tx obstruction

Answer 13

Bronchodilators

Mucolytic agents - dornase

Rehydrating agents - hypertnic, asaline

Airway clearance

Question 14

Nurtirion

Answer 14

Enteric coated pancreatic enzymes*****

May need supplements

Question 15

Type 1 and 2

Answer 15

No synthesis

Block in processing

Question 16

3,4,5

Answer 16

BLock in reg

Altered conductance

Reduced syn

Question 17

2 types of problems

Answer 17

Reduced quantity (1,2,5) - corrector

Reduced function - 3,4 - need potentiator

Question 18

Nroaml vs G551D

Answer 18

When protein binds cAMP, the chloride channel will open (normal)

in CF, might not bind the cAMP

Question 19

Ivacaftor

Answer 19

Potentiator of CFTR

Facilitates increased CL transport by potentiating channel-open probability of G551D…potentiates binding of cAMP

Question 20

Lumacaftor/Ivacvaftor

Answer 20

Indicated for CF homo for delta 508

Question 21

Most CF is caused by

Answer 21

Processeing defect (golgi problem)

Question 22

Lumacaftor

Answer 22

INcreases the amount of F508del-CFTR at the cell surface

If you add potnetiator, then it will help even more

Question 23

Most important thing in CF

Answer 23

Monitoring lung function and try to intervene as early as possible