Cystic Fibrosis Flashcards

1
Q

What is cystic fibrosis (CF)?

A

Autosomal recessive genetic condition that results in a multisystem syndrome of chronic sinopulmonary infections; malabsorption; and nutritional abnormalities. Most common life-shortening genetic disease in Caucasians in the US (1:3000)

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2
Q

Which chromosome mutation causes CF?

A

Gene that encodes for the CF transmembrane conductance regulator (CFTR) protein. On Chr. 7. Causes a deft in the ATP-binding cassette transporter gene

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3
Q

What is the most common mutation?

A

F508del. But there are more than 1500 others identified

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4
Q

How are CF gene mutations categorized?

A

5 main classes (I-V). Grouped by molecular consequences.

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5
Q

What is a class I mutation?

A

No synthesis of CFTR. Often caused by nonsense G542X

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6
Q

What is a class II mutation?

A

Block in CFTR synthesis. Often caused by AA deletion (F508del)

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7
Q

What is a class III mutation?

A

Block in gating. Often caused by missense G551D

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8
Q

What is a class IV mutation?

A

Altered conductance of CFTR. Often caused by missense R117H

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9
Q

What is a class V mutation?

A

Reduced synthesis of CFTR. Often caused by missense mut or alternative splicing

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10
Q

What effects do defects/deficiences of CFTR proteins cause?

A

Problems in salt and water movement across cell membranes; resulting in abnormally thick secretions in various organ systems

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11
Q

Why are CFTR effects in lungs often major cause of morbidity and mortality?

A

Depleted periciliary layer in the lung leads to impaired mucociliary clearance and altered host defense; critical to the pathogenesis of CF lung disease. Chronic infections with CF-related pathogens and excessive inflammatory response progressively damage the airways and lung parenchyma. Results in widespread bronchiectasis; decline in lung function; early death from respiratory failure

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12
Q

What are typical clinical features in sinus?

A

Chronic sinus infections; nasal polyps

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13
Q

What are typical clinical features in lung?

A

Recurrent respiratory infections (endobronchitis) with opportunistic bacteria (e.g. Staphylococcus aureus; Pseudomonas aeruginosa and Burkholderia cepacia); Bronchiectasis

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14
Q

What are typical clinical features in pancreas?

A

Exocrine pancreatic insufficiency (85%) - greasy; bulky; malodorous stools; failure to thrive and malabsorption nutritional consequences; CF-related diabetes

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15
Q

What are typical clinical features in GI?

A

Meconium ileus; rectal prolapse; constipation; distal ileal obstructive syndrome (DIOS)

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16
Q

What are typical clinical features in liver?

A

Cholestasis; sclerosis; cirrhosis

17
Q

What are other clinical presentations of CF?

A

Congenital absence of the vas deferens; digital clubbing on examination; sweat chloride > 60 mmol/L

18
Q

How are most newborns with CF identified in the US?

A

Most are asymptomatic and identified through newborn screening. Some (10-15%) are identified with meconium ileus. Infants with meconium ileus should be treated presumptively as having CF until a sweat test or genotyping can be obtained.

19
Q

In CO; what is our approach for newborn screening?

A

IRT/IRT/DNA. 1st screen for elevated immunoreactive trypsinogen (pancreatic enzyme). If ^ repeat IRT in 2 months. If still ^ do CF DNA panel

20
Q

What is traditional treatment of CF?

A

Historically targeted “downstream affects;” tried to manage symptoms. Requires specialized/multidisciplinary team to focus on nutrition; lung disease; antibiotic therapy; anti-inflammatory treatments

21
Q

How is nutrition in CF Pts usually treated?

A

Management of exocrine pancreatic insufficiency with enzyme supplementation; high calorie; high protein; and high fat diet; and fat soluble vitamin supplements. Also daily salt supplement due to salt loss in sweat

22
Q

How is lung disease in CF Pts usually treated?

A

Try to target cycle of mucous obstruction; airway infection; inflammatory response. Do airway clearance treatment to loosen and remove thick mucus from airways. Daily percussive therapy (Chest PT; vest therapy). Recombinant human DNAse (Pulmozyme); an inhaled mucolytic agent. Inhaled hypertonic saline. Bronchodilators. Also antibiotic therapy and anti-inflammatory treatments

23
Q

What kind of antibiotic therapy is done in CF?

A

Targets common CF related bacteria such as P. aeruginosa. Inhaled tobramycin; aztreonam. Oral or IV antibiotics

24
Q

What kind of anti-inflammatory therapy is done in CF?

A

High dose ibuprofen. Chronic azithromycin

25
Q

What new drugs are on the horizon for CF?

A

CFTR modulator. Target specific CFTR mutations.

26
Q

What is ivacaftor (kalydeco)?

A

CFTR potentiator FDA approved for people age 2 years or older with at least one G551D mutation or another gating mutation (Class III); potentially will help in partial function (Class IV and V) mutations as well

27
Q

What is Lumacaftor/ Ivacaftor (Orkambi)?

A

combination CFTR corrector and potentiator FDA approved for people ages 12 years or older with 2 copies of the F508del mutation (Class II)