Cystic Fibrosis Vignette

Question 1

1. Describe the genetics and underlying protein defect in Cystic Fibrosis (CF).
2. Describe current understanding of pathophysiology underlying CF lung disease.
3. Describe the diagnostic and therapeutic approaches in CF.

Answer 1

x

Question 2

Cystic Fibrosis (CF) is an ______ condition that results in a syndrome of chronic sinopulmonary infections and nutritional abnormalities secondary to malabsorption.

Answer 2

autosomal recessive

Question 3

CF is caused by a defect in an ATP-binding cassette transporter gene on chromosome 7 that encodes for the CF Transmembrane Conductance Regulator (CFTR) protein. The most common mutation is the:

Answer 3

F508del, although approximately 1500 other disease-causing mutations in the CF gene have been identified. CF gene is a large gene on chromosome 7

Question 4

Types of CF mutations:
I
II
III
IV
V

Answer 4

Types of CF mutations:
I - No synthesis (nonsense mutation)
II - Block in processing (F508 deletion)
III - Block in regulation (missense)
IV - Altered conductance (missense)
V - Reduced synthesis (missense)

Question 5

Typical features of CF:

Answer 5

 Greasy, bulky, malodorous stools; failure to thrive due to exocrine pancreatic insufficiency
 Recurrent respiratory infections with opportunistic bacteria (e.g. Staphylococcus aureus,
Pseudomonas aeruginosa and Burkholderia cepacia)
 Chronic sinus infections
 Digital clubbing on examination.
 Bronchiectasis
 Sweat chloride > 60 mmol/L.

Question 6

CF newborn screening Immunoreactive trypsinogen

Answer 6

false negative rate ranges from 1-5%) may present with clinical symptoms later in life.

Question 7

Pancreatic insufficiency occurs in more than ___% of persons with CF.

Answer 7

85

Question 8

Approximately 15% of newborns with CF present at birth with _____.

Answer 8

meconium ileus

[a severe intestinal obstruction resulting from inspissation of tenacious meconium in the terminal ileum.]

Question 9

From a respiratory standpoint, clinical manifestations include

Answer 9

productive cough, wheezing, chronic bronchitis and recurrent pneumonias, progressive obstructive airways disease, exercise intolerance, dyspnea, and hemoptysis.

Question 10

Chronic airway infection with bacteria, including ____ and _____, often begins in the first few months of life, even in asymptomatic infants. Eventually, _____ becomes the predominant pathogen.

Answer 10

S aureus and H influenzae; Pseudomonas aeruginosa

[Acquisition of the characteristic mucoid Pseudomonas is associated with a more rapid decline in pulmonary function. Chronic infection leads to airflow obstruction and progressive airway and lung destruction resulting in bronchiectasis.]

Question 11

Treatment: pancreatic insufficiency

Answer 11

Enzyme replacement
High fat/protein/calorie diet
Vitamin supplements
Daily salt supplement

Question 12

Treatment: airway/lungs

Answer 12

Daily percussion
Inhaled antibiotics (tobramycin (TOBI) aztreonam(Cayston)
Recombinant human DNAse (Pulmozyme - mucolytic agent)
Inhaled hypertonic saline
bronchodilators

Question 13

Anti-inflammatory treatments

Answer 13

ibuprofen

azithromycin

Question 14

CFTR modulators

Ivacaftor (CFTR potentiator)

Answer 14

G551D mutation or gating mutation. Must be older than 6

Question 15

End stage lung disease symptoms?

Answer 15

mucus plugging, bronchiectasis, inflammation, infection