Cystic Fibrosis

Front 1

What is used to induced sweating in the sweat chloride test?

Back 1

Pilocarpine

Front 2

What is always considered abnormal in a sweat chloride test?

Back 2

>60 mmol/L

When induced by Pilocarpine

*Notice differentiations in ages <6

Also confirmed by ≥ 2 CFTR mutations.

Front 3

What would ≤1 CFTR mutation in DNA testing reveal?

Back 3

Questionable CF. Expand DNA testing and sweat them again.

Pt should be followed clinically.

Front 4

What is used to treat Cystic Fibrosis related diabetes?

There is increased insulin resistance (Type 2)

There is decreased insulin production (Type 1)

Back 4

Subcutaneous Insulin.

Front 5

What is the use of Ursodiol?

Back 5

Improves essential fatty acid metabolism in liver

Front 6

What are the regulatory functions of the CFTR?

Back 6

1. Ion transport
   
2. Pulmonary inflammation
3. Bacterial adherence
4. Mucus rheology (viscosity of mucus)

Front 7

T/F: CFTR is part of the ATP Binding Cassette (ABC)?

Back 7

True

Front 8

Which secondary messenger affects CFTR?

Back 8

cAMP

Front 9

What does CFTR stand for?

Back 9

Cystic Fibrosis transmembrane conductance regulator

Front 10

How does CFTR affect ions?

Back 10

CFTR allows ions to follow electrochemical gradients. CFTR regulates the transport of:

1. Chloride
2. Bicarbonate
3. Sodium

Front 11

What is the cause of CFTR?

Back 11

A gene mutation.

Autosomal recessive gene.

Front 12

What is CFTR's general function?

Back 12

On epithelial cells sodium, and chloride are transported back into the skin while water evaporates.

Front 13

In CFTR dysfunction what occurs?

Back 13

Chloride cannot come back in

Front 14

What happens in Class I CFTR defect?

Back 14

Protein is not synthesized

Front 15

What happens in Class II CFTR defect?

Back 15

Immature CFTR are synthesized.

*Mutation of deltaF508.

Front 16

What is the most common cause of CFTR in general?

Back 16

Mutation of gene: Delta F508

A class II defect

Front 17

What occurs in Class III cystic fibrosis?

Back 17

{Activation is defected}

• Most common caused by mutation in G551D
• Dysfunctional second messenger (cAMP) activation and regulation
• CFTR is synthesized and placed in the membrane
  

Front 18

What occurs in Class IV cystic fibrosis?

Back 18

{Defective regulation of other ion channels}

CFTR is synthesized and placed in the membrane BUT...

-Chloride ion flow is reduced

Front 19

What occurs in Class V of cystic fibrosis?

Back 19

{Partial defect}

CFTR synthesis and processing is partially defective.

Front 20

What occurs in Class VI of cystic fibrosis?

Back 20

CFTR synthesized and placed in membrane

BUT...

Other ion flow is reduced.
(bicarbonate or sodium, maybe chloride)

Front 21

What is the difference between Class IV and Class VI CFTR defect?

Back 21

In both Class IV and Class V, CFTR is synthesized and placed in the membrane.

In Class IV: chloride ion flow is reduced

In Class VI: other ion flow is reduced (other than chloride. Such as bicarb, or sodium.

Front 22

Where do symptoms of CF occur?

Back 22

In one or more organ systems

#Affects epithelial cells

Front 23

How is CFTR dysfunction detected during prenatal testing?

Back 23

1. Echogenic bowel detected on fetal ultrasound
   
2. Parents carry CF trait

Front 24

What would an echogenic bowel detected on fetal ultrasound be indicative of?

Back 24

Cystic fibrosis

Front 25

What is abnormal nasal potential difference indicative of?

Back 25

Cystic fibrosis

Front 26

2 or more sweat chloride tests over 60 mmol/L is indicative of?

Back 26

Cystic fibrosis

Front 27

What disease is caused by 2 or more mutations in CFTR?t

Back 27

Cystic fibrosis

Front 28

What would be an intermediate result for a child < 6 months of age for a pilocarpine induced sweat chloride test?

Back 28

Intermediate: 30-59 mmol/L

Normal is <30 when <6 MONTHS of age

Front 29

What is considered normal results for a Pilocarpine induced sweat chloride test in a pt that is 6 years old?

Back 29

<40 mmol/L is normal for those >6 months of age

Intermediate would be 40-59 mmol/L

And >60 mmol/L is considered abnormal for all age ranges.

Front 30

What steps are taken if a patient has intermediate sweat test results and DNA testing reveals NO CFTR mutations?

Back 30

Considered questionable Cystic Fibrosis.

DNA testing is expanded.

Sweat test repeated

If <60 mmol/L the pt is followed clinically.

Intermediate sweat tests:

30-59 if <6 MOnths

40-59 if >6 MOnths

Front 31

What is the diagnosis if a pt has intermediate sweat test results, but DNA testing shows 2 CFTR mutations?

Back 31

Confirmed CF.

≥2 CFTR mutations confirms Cystic Fibrosis

Front 32

What is meconium?

Back 32

The dark green substance forming the 1st feces of a newborn infant.

Front 33

Meconium ileus is what?

Back 33

A bowel obstruction caused by blockage of the ileum of the small intestine because the baby's meconium (1st feces) is thicker and stickier than normal.

Front 34

What is the gastrointestinal presentation of CF?

Back 34

1. Meconium ileus
2. Failure to thrive
3. Steatorrhea
4. Edema (excess fluid in body cavity or tissues)
5. Hypoproteinemia (Low protein in blood)
6. Anemia (Deficient in RBC or of Hgb in blood)
7. Electrolyte balance

Front 35

What is PERT?

Back 35

Pancreatic Enzyme Replacement Therapy

Enzymes: lipase, protease, amylase.

Dosed based on lipase, units/wt of fat intake.

Coating dissolves in alkaline environment.

Front 36

What would indicate pancreatic insufficiency in fecal elastase testing?

Back 36

<200 mcg/g indicates pancreatic insufficiency

Front 37

How is Pancreatic Enzyme Replacement Therapy dosed? (PERT)

Back 37

Units/weight of Lipase enzyme or fat intake

Front 38

In which environment is lipase dissolved?

Back 38

Alkaline environments

Front 39

What should patients take PERT with?

Back 39

Fatty snacks

Max. of 2,500 U of lipase per kg per meal

Front 40

If dosing Lipase by weight. Would you give a 3 year old more units of lipase per kg per meal or a 5 year old?

Back 40

<4 yo receive more lipase with fatty snacks.

<4 yo: 1000U/kg of lipase per meal

>4 yo: 500 U/kg of lipase per meal

Front 41

What is the maximum units of lipase per kg per feeding via fat-based or weight based dosing? Per day?

Back 41

2,500 Units/ kg per feeding

10,000 units of lipase/kg per day

Front 42

When should fat-soluble vitamin replacement be started?

Back 42

With initial diagnosis of Cystic Fibrosis.

Front 43

What are the fat soluble vitamins that are replaced in CF?

Back 43

A, D, E, K

Front 44

Which gene mutation is related to Cystic Fibrosis Diabetes?

Back 44

Delta F508 Mutation

Front 45

What are the risk factors for Cystic Fibrosis-related disease?

Back 45

Advanced age

Female

Pancreatic insufficiency

Delta F508 mutation

Front 46

How is insulin affected in CF-related diabetes?

Back 46

Increased insulin resistance (DM 2)

Decreased insulin production (DM 1)

Front 47

What is the treatment for CF-related diabetes?

Back 47

Subcutaneous insulin

Front 48

Why is esophageal acid exposure higher in patients with cystic fibrosis?

Back 48

1. Decreased lower esophageal sphincter tone (LES)
2. Increased intra-abdominal pressure
3. Hyperinflated lungs
4. Chest physiotherapy

Front 49

What is the treatment for GERD in those with CF?

Back 49

1. Chest physiotherapy before meals.
   
2. Proton Pump Inhibitors
   (0.2-2 mg/kg dosed 1-2 times daily)

Front 50

What is the treatment for Meconium ileus in Cystic Fibrosis?

Back 50

Contrast enema

It is hyperosmolar, so brings water into the GI tract allowing things to move.

Breaks up meconium .

Front 51

What is the classification of 40% of Meconium ileus diagnoses?

Back 51

Complex.

Occurs in 10% of CF presentations.

Front 52

What classifies Meconium ileus as complex?

Back 52

1. Perforation
2. Atresia (absence or abnormal narrowing)
3. Meconium peritonitis (Bowel rupture)

Front 53

What osmotic laxatives are used in partial acute blockage of the ileum that is common in patients with a history of meconium ileus?

Back 53

Osmotic laxatives:

1. Polyethylene glycol
2. Gastrografin
3. Electrolyte solution

(no relationship with mutations)

Front 54

How is complete acute blockage of the ileum in DIOS treated?

Back 54

Surgery

(#Distal intestinal obstruction syndrome)

Front 55

What is the treatment for biliary cirrhosis (which leads to liver disease)?

Back 55

Ursodiol 30 mg/kg/day divided twice daily

Front 56

What is a slight elevation in alkaline phosphatase indicate?

Back 56

Liver disease

Front 57

What increases the risk of neonatal cholestasis?

Back 57

1. Hx of meconium ileus
2. prolonged parenteral nutrition
3. Increased risk of liver cirrhosis
   
   Treated with Ursodiol 30 mg/kg/day divided 2-3 times a day {VS divided 2 times in Biliary cirrhosis}

Front 58

What is the pulmonary presentation of Cystic Fibrosis?

Back 58

*Recurrent, persistent, productive cough + wheezing + bronchiolitis*

1. Recurrent cough
2. Persistent cough
3. Prolonged wheezing
4. Recurrent bronchiolitis
5. Productive cough

Front 59

What disease is directly related to lung disease severity? (Reduction in smooth muscle support system, and collapsing muscle worsens obstruction)

Back 59

Reactive airway disease

Treated with bronchodilators

Front 60

What are the chronic meds used in cystic fibrosis?

Back 60

1. Beta agonists- bronchodilators
2. Dornase alfa- nebulized qd or qod to improve mucus cleaning
3. Hypertonic saline (7%) - 4 mL nebulized BID
4. Inhaled tobramycin- 300 mg/ inhalation BID for 28 days. 1 month on, 1 month off.
5. Oral azithromycin- 200-500mcg PO 3xs weekly
6. Ivacaftor targets G551D mutations (Class 3) 150 mg PO BID with fatty foods
7. Lumacaftor- in combo with ivacaftor- 400/250 mg PO BID w fatty foods

Front 61

What are the benefits of Ivacaftor and Lumacaftor therapy?

Back 61

Ivacaftor vs Class 3 G551D mutations

Lumacaftor vs Class II Delta F508 mutations

Both...

improve pulmonary function

decreases exacerbations

increase weight gain

Require hepatic and CYP3A4 dosing reductions