Clin Med - CF

Question 1

General characteristics

Answer 1

• Most common cause of severe chronic lung disease in young adults
• Most common fatal hereditary disorder of whites in the United States

Question 2

Inheritance pattern + characteristics

Answer 2

Autosomal recessive exocrinopathy - exocrine glands produce and secrete substances onto an epithelial surface via a duct.
–Sweat, salivary, mammary, ceruminous, lacrimal, sebaceous and mucous

Question 3

What protein does CF affect?

Answer 3

Caused by abnormalities in a membrane chloride channel (the cystic fibrosis transmembrane conductance regulator [CFTR] protein)

Question 4

CF results in…

Answer 4

altered chloride transport and water flux across the surface of epithelial cells (necessary for production of thin, freely flowing mucous)

Question 5

CF Mutation

Answer 5

Mutation referred to as D F508 accounts for about 60% of cases of cystic fibrosis.

Question 6

Effect on exocrine glands

Answer 6

Almost all exocrine glands produce abnormal mucus that obstructs glands and ducts and leads to tissue damage

Question 7

Morbidity & Mortality associated with CF

Answer 7

• Attributed to respiratory compromise
• Characterized by copious hyperviscous and adherent pulmonary secretions that obstruct small and medium-sized airways
• Obstructive lung dz with chronic infection

Question 8

Symptoms

Answer 8

• Cough
• Sputum production
• Decreased exercise tolerance
• Wheezing
• Recurrent pneumonia
• Dyspnea
• Recurrent hemoptysis
• Chronic rhinosinusitis

Question 9

Clinical findings - pancreas

Answer 9

In the pancreas, the mucus prevents the release of digestive enzymes that allow the body to break down food and absorb vital nutrients

Question 10

Clinical findings - digestion

Answer 10

• Chronic malabsorption, steatorrhea (fat in the stool), diarrhea, and abdominal pain.
• Poor growth in infants (failure to thrive)
• CF related diabetes (30%)

Question 11

Clinical findings - male reproduction

Answer 11

Nearly all men with cystic fibrosis have congenital bilateral absence of the vas deferens with azoospermia

Question 12

Clinical findings on exam

Answer 12

digital clubbing,increased anteroposterior chest diameter (”barrel chest”), hyper-resonance to percussion, and apical cracklesare noted on physical examination

Question 13

Bacteria found in airway

Answer 13

• S. aureusandH. influenzae, often begins in the first few months of life.
• Eventually,Pseudomonas aeruginosaand other gram-negative bacteria become the predominant pathogens.
• -Burkholderia cepacia – Gram neg. that is very resistant to antibiotics

Question 14

Chronic infection leads to…

Answer 14

airflow obstruction and progressive airway and lung destruction

Question 15

Diagnosis - newborn screening

Answer 15

• measuring immunoreactive trypsin (IRT): a pancreatic enzyme in the blood.
• most infants with CF have elevated IRT in the newborn period, although false negative results are possible.

Question 16

Diagnosis - next step in newborn screening

Answer 16

• in positive newborn screen, the diagnosis of CF must be confirmed by sweat testing, mutation analysis, or both
• Quantitativepilocarpineiontophoresis sweat testreveals elevated sodium and chloride levels (greater than 60 mEq/L) in the sweat of patients with cystic fibrosis
• Two tests on different days are required for accurate diagnosis

Question 17

If there is high clinical suspicion, what other diagnostic tool should you use?

Answer 17

Genotyping

Question 18

Treatment

Answer 18

Conventional treatment programs focus on:

• -Clearance and reduction of lower airway secretions
• -Reversal of bronchoconstriction
• -Treatment of respiratory tract infections and airway bacterial burden
• -Pancreatic enzyme replacement
• -Nutritional and psychosocial support

Question 19

Chest Physiotherapy

Answer 19

• Postural drainage
• Chest percussion or vibration techniques
• Positive expiratory pressure (PEP) or flutter valve breathing devices
• Directed cough, and other breathing techniques

Question 20

How do PEP and flutter valve work?

Answer 20

PEP: allow air behind mucus to help move it from lung and airway walls.
Flutter: creates vibrations to move mucus.

Question 21

Medications

Answer 21

• inhaled recombinant human deoxyribonuclease (rhDNase, dornase alpha)- Pulmozyme
• inhalation of hypertonic (7%) saline twice daily
• inhaled bronchodilators

Question 22

Antibiotics & CF

Answer 22

• Short-term antibioticsare used to treat active airway infections
• S. aureus(including methicillin-resistant strains),P aeruginosa andH influenza

-Long-term antibiotic therapyis helpful in slowing disease progression and reducing exacerbations in patients with sputum cultures positive forP. aeruginosa.

Question 23

General CFTR modulator therapies MOA

Answer 23

Potentiator of the CFTR channel that works by increasing the time the channel remains open after being activated

Question 24

What is definitive treatment?

Answer 24

Lung transplantation

Question 25

Other treatments…

Answer 25

• Exogenous pancreatic enzymes
• Vaccinationagainst pneumococcal infection and annual influenza vaccination
• Screeningof family members and genetic counseling are suggested

Question 26

How does death occur?

Answer 26

from pulmonary complications (eg, pneumonia, pneumothorax) or as a result of terminal chronic respiratory failure and cor pulmonale

• median age 39
• median survival following transplantation is 7-8 years