Cystic Fibrosis

Question 1

What type of genetic condition is cystic fibrosis?

Answer 1

Autosomal recessive condition where there is a mutation on chromosome 7 in the CFFTR gene for phenylalanine , encoding for ATP-gated Cl- channel. In the sweat glands, this causes reduced absorption of Cl- and loss of sodium and water on skin surface and in the GIT, lungs and pancreas, reduced secretion of Cl-.

Question 2

On which chromosome is the CFTR gene located?

Answer 2

Chromosome 7

Question 3

What does the CFTR gene encode for?

Answer 3

ATP-gated Cl- channel

Question 4

What occurs in the sweat glands due to cystic fibrosis?

Answer 4

Reduced absorption of Cl- and loss of sodium and water

Question 5

What is a common complication in the lungs due to cystic fibrosis?

Answer 5

Lung damage and fibrosis from elastase release

Question 6

What is the Neonatal screening for cystic fibrosis?

Answer 6

heel-prick skin test.

Question 7

Which two bacteria are commonly associated with recurrent infections in cystic fibrosis?

Answer 7

• Staphylococcus aureus
• Pseudomonas aeruginosa

Question 8

What is the pathophysiology of cystic fibrosis?

Answer 8

Inflammatory response with proteases and cytokines causes lung injury, worsened by IL-8. This can result in Bronchieactasis overtime. Hypoxia can occur which results in pulmoanry hypertension and cor pulmonale

There is obstruction in pancreatic duct secretion, resulting in auto-digestion of the pancreas by digestive enzymes, increasing risk of diabetes mellitus in adults.
Thicker secretions in hepatobiliary secretions results in biliary obstruction and fibrosis.

Viscous intestinal secretions increases the risk of meconium ileus -> intestinal obstruction in neonates and adults

Majority of males are infertile due to poor development of vas deferens
Minority of female patients are infertile

Question 9

What inflammatory response is worsened by IL-8 in cystic fibrosis?

Answer 9

Lung injury

Question 10

What are the clinical signs of cystic fibrosis?

Answer 10

• Recurrent infection
• coughing
• wheezing
• disturbed sleep
  *haemoptysis
• steatorrhea
• malnutrition
  *meconium ileus in neonates causing vomiting and abdominal distention
  *clubbing and bilateral nasal polyps

Question 11

What condition can develop over time due to lung damage in cystic fibrosis?

Answer 11

Bronchiectasis

Question 12

What complication can occur due to obstruction in pancreatic duct secretion?

Answer 12

Auto-digestion of the pancreas

Question 13

What is meconium ileus?

Answer 13

Intestinal obstruction in neonates caused by thick intestinal secretions

Question 14

What is a common clinical sign of cystic fibrosis in males?

Answer 14

Infertility due to poor development of vas deferens

Question 15

What are common clinical signs of cystic fibrosis? (List at least three)

Answer 15

• Recurrent infections
• Thick cough
• GI malabsorption

Question 16

What are the complications with cystic fibrosis?

Answer 16

*Obstructive lung disease causes chronic respiratory acidosis, loss of fluid in sweat and the kidney attempts to compensate with contraction metabolic alkalosis

*Chronic inflammation of sinuses from increased mucous viscosity results in bilateral nasal polyps (soft growths), which increases the risk of pseudomonas aeruginosa infection

• Constipation and this increases risk of rectal prolapse
  Infection with Burkholderia results in poor prognsois for lung transplant
• Risk of pneumonia with pseudomonas aeruginosa
  Obstruction of biliary system, that can lead to obstructive cirrhosis and post-hepatic hyperbilirubinaemia. There is also risk of portal hypertension

*Pancreatic insufficiency assoicated with diabetes

*Clubbing and cyanosis

*Electrolyte abnormalities with low sodium, chloride and potassium with possible metabolic acidosis

Question 17

What is CFTR-related diabetes?

Answer 17

Cystic fibrosis related diabetes occurs due to abnormal glucose metabolism, due to CFTR mutation causing abnromal beta-cell function and structural damage from the auto-digestion of the pancreas, resulting in cyst formation and progressive fibrosis. First indication is failure to maintain or gain weight, with polyuria and polydipsia being less common.

Management is withn insulin therapy similar to type 1 diabetes using insulin doses for meals, with rapid-acting insulin and long-acting insulin. Thy rarely present with diabetic ketoacidosis and have lower insulin requirements than type 1 diabetics

Question 18

Which airway condition are patients with cystic fibrosis at greater risk for?

Answer 18

Cystic fibrosis pulmonary sepsis is at greater risk in these patinets due to airways chronically colonised by pathogenic bacteria from an early age, due to impaired mucociliary clearance which can result in dyspnoea, increased volume of purulent sputum, haemoptysis, wheeze and chest ache. FEV1 levels are a marker for infection and decreases during these periods and improve with antibiotic therapy.

Question 19

How does cystic fibrosis change with age?

Answer 19

There is a progression of airway colonisation over time, as organisms become more resistant to antibiotic from staphylococcus aureus, haemophilius influenzae and pseudomonas aeruginosa.

Most patients with CF by their early teens are chronically infected with pseudomonas aeruginosa intermittently. They are at more risk of respiratory infection with non-tuberculous mycobacteria abscessus, typically found in the environment.

Question 20

How is cystic fibrosis diagnosed?

Answer 20

*Evidence of dysfunctional CFTR gene variants
*Heel prick immunoreactive trypsinogen newbornscrenening
Sweat testing for chloride, pancreatic elastase to measure disease progression
*CT imaging and spirometry
*Bronchoalveolar lavage will show high neutrophil count, due to inflammation from mucus obstruction
*Pulmonary function tests showing low FEV1/FVC ratio
*Regular physical exercise

Question 21

What is the purpose of sweat testing in cystic fibrosis diagnosis?

Answer 21

To measure chloride levels

Question 22

How is cystic fibrosis managed?

Answer 22

Management of cystic fibrosis surrounds maintaining lung function, nutritional support, GI screening for biliary cirrhosis and portal hypertension includes
vaccination and screening for diabetes.
airway clearance with nebuliser hypertonic saline and chest physiotherpay
Pulmonary management for acute cystic fibrosis exacerbation with pseudomonas aeruginosa using fluroquinolones such as ciprofloxacin

nutritional support and laxatives for constipation

pancreatic enzyme replacement
Optimising breathing with nasal cannula oxygen supplementation to improve exercise insurance and sleep quality

Question 23

What is the typical FEV1/FVC ratio in cystic fibrosis patients?

Answer 23

Low

Question 24

What is a key aspect of management for cystic fibrosis?

Answer 24

Maintaining lung function

Question 25

What dietary recommendations are made for cystic fibrosis patients?

Answer 25

High-fat diet with fat-soluble vitamins

Question 26

What is the risk of Burkholderia cepacia infection in cystic fibrosis patients?

Answer 26

Poor prognosis for lung transplant and causes rapid decline in lung function and health. The subtype Burkholderia cepacia can act as an exclusion criteria for lung transplant so it is essential that these patient groups are separated from non-colonised patinets due to high risk of transmission and risk of cepacia syndrome.

It has strong antibiotic resistance and proliferates in water-based environments which contaminates pharmaceuticals.

Question 27

What is the treatment for burkholderia cepacia?

Answer 27

Burkholderia cepacia is typically resistant to antibiotics, so combination IV antibiotics therapy with 2-3 different classes like ceftazidime and aminoglycoside.

Question 28

What is Cepacia syndrome?

Answer 28

Acute necrotizing pneumonia with worsening respiratory allure that can evolve into acute respiratory distress syndrome and bacteraemia. It is caused by the strain Burkholderia cenocepacia

Question 29

What is cystic fibrosis related diabetes caused by?

Answer 29

Abnormal glucose metabolism due to CFTR mutation

Question 30

What is the first indication of cystic fibrosis related diabetes?

Answer 30

Failure to maintain or gain weight

Question 31

What is the primary treatment for cystic fibrosis pulmonary sepsis?

Answer 31

Antibiotic therapy

Question 32

What is the most common pathogen that patients with cystic fibrosis experience?

Answer 32

pseudomonas aeruginosa Which should be treated with oral antibiotic Fluoroquinolone such as ciprofloxacin

Question 33

What is the chronic management of pseudomonas aeruginosa?

Answer 33

Chronic management of pseudomonas aeruginosa infection is with twice daily nebulised colistin and alternatively, aminoglycosides. First instance of pseudomonas infection should be treated aggressively with oral ciprofloxacin for 4-6 weeks followed by 6 weeks of colistin.

Question 34

What are the complications of cystic fibrosis? (List at least three)

Answer 34

• Chronic respiratory acidosis
• Obstructive cirrhosis
• Pancreatic insufficiency

Question 35

What is the primary goal of physiotherapy in cystic fibrosis management?

Answer 35

Physiotherpay involves active cycle breathing control and positive expiratory pressure masks to build up expiratory function of lungs and improves aerobic capacity. Later stage of disease invovles respiratory failure and cor pulmonale so long term oxygen may be required and steroids to improve lung function.

Question 36

How are exacerbations in cystic fibrosis diagnosed?

Answer 36

Exacerbations are diagnosed based on increase in productive cough, change in sputum appearance/volume, new signs on auscultation, CXR signs, decreased appetite, fall in FEV1.

Question 37

What is the risk of spontaneous pneumothorax in cystic fibrosis?

Answer 37

More common in male patients

Question 38

What are the nutritional needs for cystic fibrosis patients with pancreatic insufficiency?

Answer 38

Supplementation with vitamins A, D, E, and K

Question 39

When are patients considered for transplantation?

Answer 39

Patients are considered for transplantation when life expectancy is less than 2 years, and an FEV1 less than 30% with rapid progressive deterioration, hypoxia and hypercapnia..

Question 40

What should be monitored for liver health in cystic fibrosis patients?

Answer 40

Bile production and biliary obstruction and cirrhosis as blood tests are not sensitive.

Question 41

How are patients with cystic fibrosis undergoing therapy managed?

Answer 41

Patients with cystic fibrosis undergoing surgery should receive prophylactic antibiotic therapy, and port-a-Cath can be administered for patinets requiring frequent courses of IV antibiotics. There is a major risk of antibiotic sensitivity with repeated antibiotic courses, so desensitisation regimes are important.

Question 42

How should pancreatitis be managed in cystic fibrosis?

Answer 42

Pancreatitis should be treated with PPI, IV rehydration and bowel rest.