CF

Question 0

??

Answer 0

Chloride ion channel

Apical membrane of epithelial cells

Question 1

Chromosome for CF

Answer 1

CFTR gene on chromosome 7 long arm

Question 2

How do you diagnose CF?

Answer 2

Need 1+ typical phenotypic features of CF, sibling with CF, or positive newborn screening
THEN… you need lab confirmation
2 + sweat chloride tests, 2 known disease causing CFTR mutations, abnormal nasal potential different.

Question 3

What is the median age at diagnosis?

Answer 3

5.3 months
Meconium ileus: 0.2 month
newborn screening: 0.5 month
Symptoms: 14.5 months
Increased risk of complications in patients diagnosed by symptoms vs NBS.

Question 4

Respiratory Disease in CF

Answer 4

Lung infection & inflammation cycle damage the lungs and decrease lung function (FEV1)
Incidence of pulmonary exacerbations increase with age.
Progressive lung disease is the leading cause of death in CF patients.

Question 5

Pulmonary Manifestations of CF

Answer 5

Chronic cough, sputum production, recurrent infections, bronchiectasis, hemoptysis, pneumothorax, allergic bronchopulmonary aspergillosis (we breath this fungus in every day) pulmonary arterial hypertension, respiratory insufficiency/failure

Question 6

Pathogenesis of Lung Disease in CF

Answer 6

Abnormal CFTR gene, abnormal CFTR protein, abnormal salt transport, abnormal mucus, impaired clearance, infection, inflammatory response, bronchiectasis… (diagram in lecture slides)

Question 7

Most common respiratory infections in CF?

Answer 7

Staph and then Pseudomonas later in life

Question 8

Therapeutic Approaches to CF

Answer 8

Depends on the stage:
Genetic mutation -> Protein rescue/activation -> proper ion transport -> anti infective anti inflammatory -> transplanation.
A lot of research is being done with genetic replacement therapy but not much success.

Question 9

Positive Sweat Test Result

Answer 9

> 60 mmol/L -> Consistent with CF

40-60 mmol/L -> borderline-further investigation warranted

Question 10

Nasal Potential Difference

Answer 10

Measures chloride ion secretion of CFTR protein after isoproterenol challenge
Absent in CF nasal epithelium
Technically challenging! -> lab must do regularly to be good at it.

Question 11

Newborn Screen

Answer 11

Immunoreactive trypsinogen (IRT): cutoff varies by state
second test: IRT, DNA
numerous false positives and also picks up carriers.

Question 12

IRT/DNA approach

Answer 12

immunoreactive trypsinogen (pancreative enzyme precursor, elevated in CF patients) -> mutant analysis (F508del or a panel of mutations) -> sweat test

Question 13

Staph aureus in CF patients

Answer 13

Gram + cocci
Most commonly found isolate in CF
Now have to worry about Methicillin Resistant Staph Aureus (MRSA)
Treatment: MSSA: naficillin, cefazolin, oxacillin
MRSA: vancomycin, septra, clindamycin, linezolid
MRSA is associated with decreased survival

Question 14

CF and Burkholderia cepacia Complex

Answer 14

Formerly classified as pseudomonas, but now a complex (BCC) of different genomovars.
usually far in progression of CF
may be colonization or active infection
Usually highly resistant to many antiobiotics

Question 15

What is Cepacia Syndrome?

Answer 15

End stage lung function with fevers, weight loss, feeling bad

Question 16

Pseudomonas aeruginosa

Answer 16

Infection occurs as early as first year of life
Prevalence increases with age -> more than 73% of adult are chronically infected.
Chronic infection with P. aer. is an independent risk factor for accelerated …. (slide)

Question 17

What is the mucoid phenotype associated with CF patients?

Answer 17

With prolonged infection, P. aeruginosa converts to a mucoid phenotype by the production of alginate. Mucoid phenotype is seen infrequently in pop without CF.
Conversion of P. aeruginosa to the mucoid phenotype worsens prognosis.

Question 18

Pseudomonas aeruginosa

Answer 18

Gram negative rod
Catalase positive, oxidase positive
aerobic
flagella provide motility
antibiotic resistance ranges from sensitive to pan-resistant
Questions on boards often say it “smells like grapes or blue tortilla chips in the lab”

Question 19

How do we treat CF patients with pseudomonas infection? What is meant by “double covering”

Answer 19

Generally in CF, will “double cover”
Pseudomonas to help prevent resistance
One antibiotic from two different classes with differing MOA
ex. one cell wall active agent, one ribosome directed agent
Using two drugs that work in the same manner is NOT double covering!

Question 20

Why do CF patients require very high doses of antibiotics?

Answer 20

Lung pathology

CF patients are HYPER metabolic and often very thin

Question 21

All anti-pseudomonal drugs are IV expect for which ones?

Answer 21

flouroquinolones

Question 22

How do you test for Pancreatic insufficiency? (PI)

Answer 22

Fecal elastase levels < 200 mcg/gm
72 hr stool sample with dietary inventory
Fat excretion > 7% of intake is abnormal
Secretin stimulation test

Question 23

PERT for pancreatic insufficiency

Answer 23

varying amt of lipase, protease and amylase
granules/microspheres coated with pH sensitive material
improves fecal fat absorption in pts with PI
Acid suppression increases efficacy of enzymes

Question 24

Meconium ileus

Answer 24

earliest clinical manifestation of CF
Meconium -> inc albumin and dec water content, combined with thick mucus, becomes thicker viscous texture, inspissation of meconium, partial or total obstruction -> end up with microcolon

Question 25

DIOS?

Answer 25

Distal intestinal obstruction syndrome
acute complete or partial obstruction of iliocecum
Diagnosis is made clinically
-acute abdominal pain, palpable RLQ mass

Question 26

Intussusception - GI manifestation with CF patient

Answer 26

Similar risk factors to DIOS with inspissated bowel serving as lead point.
May present with colicky ab pain bilious vomiting rectal bleeding
Water soluble contrast enema may be more effective than air.

Question 27

Rectal prolapse?

Answer 27

Develops from Intussusception of rectum

occurs in 20% of CF patients 6 mo-2 yrs

Question 28

SIBO (small intestinal bacterial overgrowth)

Answer 28

Abnormally increased # bacteria in upper GI
transforms nutrients into nonabsorbable and toxic substances
Contributes to fat malabsorption and malnutrition by deconjugating biile salts, interferes with ability to…

Question 29

Diagnose SIBO?

Answer 29

diagnosed with symptoms (bloating gassiness flatulence ab pain)
can be diagnosed with H2 breath test
empiric treatment often appropriate.