Cystic Fibrosis

Question 1

Where is the CFTR present?

Answer 1

in epithelial cells (pancreas, salivary glands, sweat glands, respiratory tract, reproductive tract)

Question 2

Where is the CFTR gene located?

Answer 2

long arm of chromosome 7

Question 3

What are the different broad functions of the CFTR?

Answer 3

• ATP regulated chloride channel

- Regulatory protein for other channels

Question 4

The functions of the CFTR are ______ specific.

Answer 4

tissue

Question 5

True or false: The CFTR can also function as an ENaC channel.

Answer 5

True!

Question 6

Mutations in CFTR are closely linked to ________ and _______, but not to ________.

Answer 6

infertility; pancreatic function; pulmonary function

Question 7

What is the most common CFTR mutation?

Answer 7

3 base deletion at position 508, removing a phenylalanine (ΔF508)

Question 8

Which CFTR mutation class is the most severe vs. least?

Answer 8

• Most: Class I (no functional CFTR is created)

- Least: Class V (normal CFTR protein is created and moves to cell surface but in insufficient quantities)

Question 9

Which class of CFTR mutation is the most common?

Answer 9

Class II (CFTR protein is created but is misfolded, so it does not move to the cell surface)

Question 10

What are the 2 models explaining how CFTR mutations lead to clinical manifestations of CF?

Answer 10

• High salt model: Cl- cannot be reabsorbed in the sweat glands, so Na+ and water reabsorption are also decreased and ASL becomes salty
• Low volume model: CFTR mutation leads to lack of regulation of ENac, so Na+ is hyperabsorbed; water flows passively, and low volume of ASL leads to increased mucus concentrations

Question 11

How does CF show up on CXR?

Answer 11

• Upper lobe predominant bronchiectasis (signet ring and tram tracking)
• Peribronchial cuffing
• Nodules/mucus impaction
• Blebs/cysts

Question 12

What is the most common cause of respiratory infection in CF patients in childhood vs. adulthood?

Answer 12

• Childhood/early adulthood: S. aureus

- Adulthood: P. aeruginosa

Question 13

Which causative agent of respiratory infections in CF is associated with rapid decline?

Answer 13

Burkholderia cepacia (genomovar III)

Question 14

What are the sinus effects of CF?

Answer 14

• Hypertrophy/hyperplasia of secretory elements
• Inflammation/edema
• Polyps
• Transepithelial electric potential raised

Question 15

What are the GI tract effects of CF?

Answer 15

• Meconium ileus
• Focal biliary cirrhosis
• Fatty liver
• Hypoplastic gallbladder & gallstones
• Distal intestinal obstruction syndrome
• Rectal prolapse

Question 16

What are the pancreatic effects of CF?

Answer 16

• Obstruction of ducts with inspissated secretions leading to dilation, destruction, fibrosis
• Exocrine insufficiency/fat malabsorption

Question 17

What are the bone and joint diseases associated with CF?

Answer 17

osteopenia and osteoporosis in 40-60% (due to Vit. D deficiency, Ca malabsorption, accelerated bone loss)

Question 18

What is CF Related Diabetes?

Answer 18

• Pancreatic endocrine insufficiency
• Symptoms=polyuria, polydipsia, weight loss, unexplained drop in lung function
• Screen yearly

Question 19

What are the genitourinary effects of CF in males vs. females?

Answer 19

• Males: CBAVD (failure of sperm transport, not production), 98% infertility rate
• Females: endocervicitis, anovulation, 20% infertility rate

Question 20

What are the symptoms of pancreatic exocrine insufficiency and how is it treated?

Answer 20

• Symptoms: steatorrhea, malabsorption, inability to gain weight, deficiency of Vitamins ADEK
• Treated with enzyme replacement

Question 21

What are the 2 main tests used to diagnose CF?

Answer 21

• Sweat test (40-60 borderline, >60 abnormal)

- Genetic test

Question 22

What does newborn screening for CF involve?

Answer 22

blood test, sweat test, mutation panel

Question 23

In which population is genotyping the most effective?

Answer 23

Caucasians with typical disease (less effective in the non-white population with a non-classic phenotype)

Question 24

What are the variety of treatment options available for CF?

Answer 24

• Antibiotics
• Airway clearance
• Bronchodilators
• Anti-inflammatory drugs
• Mucolytics
• Lung transplant

Question 25

Which formulation of antibiotics is the best for CF patients/

Answer 25

cycled, nebulized antibiotics (can deliver higher concentration in airways without the typical side effects)

Question 26

What is TOBI?

Answer 26

inhaled preservative free tobramycin

Question 27

What is azithromycin used for in CF?

Answer 27

It is used for its anti-inflammatory effects more than its antimicrobial effects.

Question 28

What is rhDNAse?

Answer 28

it is a mucolytic that works by chopping up extracellular DNA from WBCs, which composes up to 10% of CF secretions

Question 29

What is the mutation specific therapy used to treat CF?

Answer 29

• Potentiators: Ivacaftor (works on class III-V mutations and helps CFTR open)
• Correctors/chaperones: Lumacaftor (works on class II mutations and helps protein fold properly)

Question 30

How does nutrition play a role in CF?

Answer 30

• Increased caloric demand due to chronic infection
• Malabsorption
• CFRD
• Good nutritional status and weight >50th percentile associated with better outcomes

Question 31

CF is the _____ most common indication for lung transplant.

Answer 31

3rd

Question 32

When should you refer a CF patient for lung transplant?

Answer 32

when FEV1 is <30% predicted

Question 33

median age of CF diagnosis?

Answer 33

6 months