CF: Clinical Aspects and Pathophysiology

Question 1

Inheritance Pattern of CF and the carrier rate

Answer 1

Autosomal Recessive

1 in 25

Question 2

Incidence of CF

Answer 2

1 in 2500 live births

(300 new cases/year in UK)

Question 3

What is the function of the CFTR gene

Answer 3

Codes for CFTR protein which is a caMP-regulated Cl- and HCO3- channel at apical membrane of epithelial cells

Regulates ENaC too

Question 4

How could CF lead to respiratory failure?

Answer 4

Decreased clearance of mucus

Increase infections and inflammation

Small airway plugging

Bronchiectasis

Respiratory failure

Question 5

CF is a multi-organ disease. What are its other extrapulmonary presentations

Answer 5

• Sinus infections and Nasal Polyps
• Bile duct obstruction
  
  • Biliary cirrhosis
• Exocrine pancreatic insufficiency
  
  • Malnutrition
• Infertility
  
  • CBAVD in men

Question 6

What are the 6 classes of CFTR mutations

Answer 6

• I - no CFTR synthesis
• II - Synthesis but no processing
• III - Block in gating
• IV - altered conductance
• V - reduced synthesis
• VI - increased recycling

Question 7

About how much CFTR is enough to decrease sypmtoms

Answer 7

30%

Question 8

What are the broad categories of therapies that have been developed to treat CF

Answer 8

• CFTR protein correctors/potentiators
• Mucolytics
• Anti-inflammatories
• Anti-microbial
• Nutrition

Question 9

What are the two approaches to restoring CFTR function

Answer 9

• Potentiators
  
  • Increase ion flow through CFTR on membrant
• Correctors
  
  • Corrects the misfolding of CFTR to increase its processing and delivery to membrane

Question 10

What are the diagnostic tests for CF

Answer 10

• Sweat Test
• CFTR Genotyping
• Stool Elastase
  
  • Pancreatic insufficiency
• Nasal Potential Difference
  
  • Measure of ion transport
  • Only i specialist centres

Question 11

What are the ranges for sweat test

Answer 11

Question 12

What are some symptoms of CF

Answer 12

• Cough with sputum
• Wheeze
• Recurrent Infections

Question 13

What are some signs of CF

Answer 13

• Nasal polyps
• Finger clubbing
• Malnutrition

Question 14

What are the aims of modern CF management

Answer 14

• Maintain pulmonary health
  
  • Asymptomatic
  • ↓Infections
  • Normal lung function
  • ↓Exacerbations
• Normal growth/nutrition
• QoL
• Fulfill potential
  
  • Social
  • Academic
  • Financial

Question 15

What can we use to assess respiratory disease

Answer 15

• Physical Examination
• Microbiology
• Radiology
  
  • CXR
  • FRCT
  • Ventilation Scan
• Physiology
  
  • Oximetry
  • Spirometry
• Bronchoscopy

Question 16

What is the advantage of spirometry in assessing CF disease

Answer 16

• Reproducible measure of lung volumes

Question 17

What are some disadvantages of spirometry in assessing CF

Answer 17

• Limited normal values for <5 years
• Relatively insensitive
  
  • Normal LFT even with evolving CF disease

Question 18

OUtline how Lung Clearance Index is measured

Answer 18

• Known concentration of inert gas inhaled
  
  • Until equilibrium
• Patient exhales and inert gas concentration measured in exhaled breath

Question 19

What is a limitation of microbiology samples from CF and what is the implication of this?

Answer 19

Paediatric patients may not be able to expectorate

Could miss P**seudomonas aeruginosa antibodies -> produce biofilm and treatment wouldn’t work

Question 20

What pathogens are usually found in CF patients

Answer 20

• Staphylococcus
  
  • ​Protocol: Babies given prophylactic flucoxacillin
• Pseudomonas aeruginosa

Question 21

Features of Pseudomonas aeruginosa

Answer 21

• Oppostunistic
• Grame negative
• Planktonic or biofilm form

Question 22

What is the role of bronchoscopy in CF

Answer 22

• Microbiological samples
  
  • Non-expectorating patients
• Clearnce of mucus plugs
• Research

Question 23

What is a potential novel therapy against antibiotic resistance

Answer 23

Bacteriophages

Question 24

What are some features of bacteriophages

Answer 24

Virus that is highly specific to a bacteria

Self-amplifying

Self-limiting

No reported adverse effects

Question 25

What is the mechanism of action of bacteriophages

Answer 25

• Attachment
  
  • Phage lands on target bacterium wall
• Phage DNA
  
  • Is injected into bacterium by the sheathing of phage tail
• Phage genome replication
  
  • Replication of DNA
  • Taking over bacterium’s metabolic machinery
• Synthesis
  
  • Production of phage components
• Assembly
• Release
  
  • Phage enzyme breaks down peptidoglycan
  • Cell wall lysis

Question 26

What are some gastrointestinal complications of CF

Answer 26

• Exocrine and endocrine pancreatic insufficiency
• GORD
• Meconium ileus
• Constipation
• Liver disease

Question 27

How do you treat GI involvement

Answer 27

• Improve Fat absorption
  
  • PERT (Pancreatic Enzyme Replacement Therapy)
• Increase intake
  
  • Calories
  • Fat
• Supplemental Diet
  
  • DEKAs
  • Feeds/gastrostomy