Cystic Fibrosis

Question 1

What is CF?

Answer 1

CF stands for Cystic Fibrosis.

Question 2

What is the commonest inherited genetic condition in the UK?

Answer 2

Cystic Fibrosis is the commonest inherited genetic condition in the UK.

Question 3

How is CF inherited?

Answer 3

CF is inherited in an autosomal recessive manner.

Question 4

What is the carrier frequency of CF?

Answer 4

Approximately 1 in 25 individuals are carriers of CF.

Question 5

What is the incidence of CF in births?

Answer 5

CF occurs in approximately 1 in 2500 births.

Question 6

Which population does CF primarily affect?

Answer 6

CF primarily affects the Caucasian population, with 97% of cases occurring in this population.

Question 7

What protein does the CF gene code for?

Answer 7

The CF gene located on chromosome 7q31 codes for a protein called Cystic Fibrosis Transmembrane Regulator Protein (CFTR).

Question 8

What is the most common CF mutation?

Answer 8

The most common CF mutation is ∆F508.

Question 9

How many different CF mutations are there approximately?

Answer 9

There are approximately 1700 different CF mutations.

Question 10

How many individuals with CF are estimated to be in the UK?

Answer 10

Approximately 9000 individuals are estimated to have CF in the UK.

Question 11

Where is the CFTR protein located?

Answer 11

The CFTR protein is located in the membrane of epithelial cells.

Question 12

What is the function of the CFTR protein?

Answer 12

The CFTR protein regulates the transport of chloride ions by activating cyclic adenosine monophosphate (cAMP) and calcium-activated chloride channels.

Question 13

What is the role of CFTR in sodium transport?

Answer 13

CFTR inhibits the transport of sodium through the sodium channels in the epithelial cell membrane.

Question 14

How does CFTR regulate the movement of bicarbonate anions?

Answer 14

CFTR plays a role in regulating the movement of bicarbonate anions.

Question 15

Which chromosome is the CF gene located on?

Answer 15

The CF gene is located on the long arm of chromosome 7.

Question 16

What happens to chloride ions in airway epithelial cells in CF?

Answer 16

In CF, faulty CFTR affects chloride channels, leading to chloride ions building up in the cell.

Question 17

What is the consequence of chloride buildup in CF cells?

Answer 17

The buildup of chloride ions in CF cells creates a negative charge that attracts sodium ions into the cell.

Question 18

How does sodium ion movement contribute to CF-related issues?

Answer 18

Sodium ions, along with water, move into the CF cells due to the negative charge, resulting in dehydration of the mucous.

Question 19

What happens to the mucous in CF due to faulty CFTR?

Answer 19

The mucous becomes dry and thick due to the impaired movement of water caused by faulty CFTR.

Question 20

What is the role of the muco-ciliary escalator?

Answer 20

The impairment of the muco-ciliary escalator in CF leads to difficulties in the functioning of the cilia, which are responsible for clearing mucus from the airways.

Question 21

What is the role of CFTR in the cell membrane?

Answer 21

CFTR serves as a chloride channel in the cell membrane.

Question 22

Where is the CFTR protein synthesized?

Answer 22

The synthesis of CFTR protein occurs in the endoplasmic reticulum.

Question 23

What processes are involved in CFTR protein production and maturation?

Answer 23

CFTR undergoes protein translation, processing, and trafficking before being inserted into the cell membrane.

Question 24

What is the CFTR gene involved in?

Answer 24

The CFTR gene is responsible for gene transcription, leading to the production of CFTR protein.

Question 25

What is the function of the Golgi apparatus in CFTR processing?

Answer 25

The Golgi apparatus plays a role in the processing and maturation of CFTR protein.

Question 26

What are the different classes of CFTR mutations?

Answer 26

Class 4 mutations result in faulty CFTR ion channels, Class 3 mutations lead to poor CFTR function, Class 2 mutations cause misfolding of CFTR (e.g., ∆F508 mutation), and Class 1 mutations result in the absence of CFTR.

Question 27

What is the impact of abnormal CFTR on chloride and sodium reabsorption?

Answer 27

Abnormal CFTR protein leads to decreased chloride reabsorption and increased sodium reabsorption.

Question 28

How does abnormal CFTR affect the viscosity and water content of secretions?

Answer 28

Secretions in CF have a very high viscosity and reduced water content due to abnormal CFTR, making them thick and sticky.

Question 29

What is the consequence of thick and stagnant respiratory secretions?

Answer 29

Thick and stagnant respiratory secretions impede mucociliary clearance in the bronchi, leading to difficulties in clearing mucus from the airways.

Question 30

What is the effect of abnormal CFTR on defense against respiratory infections?

Answer 30

The decreased defense against respiratory infections is a result of the impaired clearance of mucus and the altered respiratory secretions caused by abnormal CFTR.

Question 31

Which organs are affected by CF?

Answer 31

Respiratory System:

Bronchiectasis (permanent dilation of bronchial tubes)
Recurrent respiratory infections
Respiratory failure
Gastrointestinal System:

Pancreatic insufficiency (impaired enzyme production)
Diabetes mellitus (due to pancreatic dysfunction)
Skin:

Increased sweat production
Reproductive System:

Infertility (mainly in males due to blockage of the vas deferens)

Question 32

What are the symptoms of respiratory tract involvement in CF?

Answer 32

Upper Respiratory Tract:

Chronic sinus disease
Nasal polyps
Lower Respiratory Tract:

Chronic cough and sputum production
Bronchiectasis (dilated and inflamed bronchi)
Chronic suppurative lung disease (presence of pus)
Colonization with bacteria
Frequent respiratory infections
Clubbing (widening and rounding of the fingertips)
These symptoms are commonly observed in individuals with CF and are a result of the sticky mucous, airway obstruction, infection, inflammation, and subsequent lung damage caused by the defective CF gene and decreased chloride secretion.

Question 33

Which organisms are commonly associated with respiratory infections in CF?

Answer 33

Staphylococcus aureus
Haemophilus influenzae
Pseudomonas aeruginosa (Gram-negative bacteria)
Burkholderia cepacia (Gram-negative bacteria)
What is meant by colonization in CF?
Colonization refers to the presence and persistence of these bacteria in the respiratory system of individuals with CF. Once established, these bacteria can be difficult to eradicate.

Question 34

How do frequent respiratory infections affect the chest X-ray findings in CF?

Answer 34

Frequent respiratory infections can lead to significant lung damage in CF, resulting in abnormal chest X-ray findings such as bronchiectasis (permanent dilation of bronchial tubes). These abnormalities are often observed on chest X-rays of individuals with CF.

Question 35

What is the impact of CF on the gastrointestinal (GI) tract?

Answer 35

Pancreas:

Abnormal chloride transport due to defective CFTR results in the destruction of the pancreas and exocrine insufficiency.
Decreased lipase activity impairs fat digestion.
Reduced absorption of fat in the small intestine leads to steatorrhea (pale, floating stool).
Decreased water content in the intestines results in the formation of thick fecal material, causing intestinal obstruction. This can be equivalent to meconium ileus in neonates.
Intestines:

Sticky secretions in the intestines can cause obstruction.

Question 36

What are the consequences of the lack of fat absorption in CF?

Answer 36

Nutritional deficiencies, including a decrease in fat-soluble vitamins.
Failure to thrive (FTT) in children.
How does CF affect the endocrine function of the pancreas?
CF can lead to the failure of endocrine pancreatic function, resulting in the development of diabetes mellitus.

Question 37

Are there any other GI complications associated with CF?

Answer 37

Yes, CF can also lead to liver cirrhosis in some cases.

Question 38

What are the common presentations of CF in newborns?

Answer 38

Meconium ileus: Obstruction of the intestine due to thick, sticky meconium.
Failure to thrive (FTT): Difficulty gaining weight and growing properly.
Recurrent respiratory infections: Frequent respiratory infections, such as pneumonia or bronchitis.

Question 39

What are some other impacts of CF?

Answer 39

Infertility: Both males and females with CF may experience infertility.
Azoospermi Complete absence of sperm in semen in males.
Sub-fertility: Reduced fertility in both males and females.
Psychological: CF can have psychological effects due to the chronic nature of the condition and its impact on daily life.
Social: CF may require significant medical care and lifestyle adjustments, which can affect social interactions and relationships.

Question 40

What are the different screening methods for CF?

Answer 40

Antenatal:

Carrier testing and genetic counseling for individuals planning to have children.
Prenatal:

DNA analysis on a sample of chorionic villus obtained through chorionic villus sampling (CVS) or amniocentesis.
These tests allow for reproductive decision making based on the presence or absence of CF-related genetic mutations in the fetus.
Neonatal (newborn screening):

Guthrie test (bloodspot test): Screens for various genetic conditions, including CF.
Sweat test: Confirms the diagnosis of CF by measuring chloride levels in sweat.
Early diagnosis through newborn screening allows for timely intervention and improved outcomes.

Question 41

How is CF diagnosed?

Answer 41

Clinical Presentation:

Evaluation of symptoms such as recurrent respiratory infections, meconium ileus, and failure to thrive (FTT).
Sweat Test:

A sweat test measures the chloride content in sweat. A chloride level higher than 60 mmol/L is considered abnormal and indicative of CF.
Abnormal Potential Difference:

Measurement of the abnormal potential difference across the nasal epithelium can help support the diagnosis of CF.
DNA Analysis:

Genotyping for common CF mutations is performed to detect specific genetic variations associated with CF.
Chest X-ray:

Chest X-rays are often performed and can show abnormalities such as bronchiectasis, a hallmark of CF lung disease.

Question 42

Why is there an elevated chloride level in the sweat of individuals with CF?

Answer 42

In individuals with CF, the defective CFTR protein results in a malfunctioning chloride channel in the sweat glands. As a result, chloride ions are unable to be properly transported out of the cells and into the sweat. This leads to the accumulation of chloride ions in the sweat, resulting in a high chloride concentration in the sweat of individuals with CF. The elevated chloride level in the sweat is a characteristic finding on the sweat test, which is used as a diagnostic tool for CF.

Question 43

What is the role of a specialist CF center in the management of CF?

Answer 43

Doctors: CF specialists who oversee the medical management and treatment plans.
CF Nurse Specialists: Nurses specialized in CF care who provide ongoing support, education, and coordination of care for patients.
Physiotherapists: Provide chest physiotherapy techniques and exercises to help mobilize and clear mucus from the lungs.
Occupational Therapists: Assist in managing daily activities and provide strategies for maintaining optimal lung function and quality of life.
Dieticians: Offer nutritional assessment and guidance to ensure adequate calorie intake, pancreatic enzyme replacement therapy, and management of malnutrition.
Psychologists: Support the mental health and well-being of individuals with CF and their families, helping them cope with the emotional challenges of the condition.
Teachers/Schools: Collaborate with CF teams to support educational needs and accommodations for children with CF.
Support for Family: Provide counseling, education, and resources to support the family members of individuals with CF.
CF Trust: A charitable organization that offers information, support, and advocacy for people with CF and their families.

Question 44

What are the treatment options for respiratory disease in CF?

Answer 44

Prompt Antibiotics: Administering antibiotics promptly to treat respiratory infections and prevent complications.
Intense Chest Physiotherapy: Regular and vigorous chest physiotherapy techniques to help clear mucus from the lungs.
Nebulized DNAse: A medication that helps degrade high concentrations of DNA in respiratory secretions, reducing their viscosity and improving clearance.
Mucolytic Drugs: Medications that help thin and loosen mucus, making it easier to clear from the airways.
Bronchodilators: Medications that help relax the airway muscles, improving airflow and easing breathing.
Long-Term Oxygen Therapy (LTOT): Administering oxygen to individuals with severe respiratory insufficiency to improve oxygenation.
Lung or Heart and Lung Transplantation: For individuals with end-stage lung disease, transplantation may be considered as a treatment option.
New Treatments: Ongoing research and development have led to the introduction of new therapies specifically targeted at CF, such as CFTR modulator drugs that address the underlying genetic defect in CF.

Question 45

How is pancreatic disease managed in individuals with CF?

Answer 45

Exocrine Pancreatic Insufficiency:

Creon (pancreatic enzyme replacement therapy): Oral pancreatic enzymes are prescribed to aid in digestion and compensate for the lack of pancreatic enzymes. These enzymes help break down fats, proteins, and carbohydrates.
Multivitamins: Since fat-soluble vitamin absorption may be impaired, individuals with CF are often prescribed multivitamin supplements to ensure adequate levels of vitamins A, D, E, and K.
Nutritional Support: In cases of severe malnutrition or inadequate oral intake, enteral feeding (tube feeding) may be recommended to ensure sufficient calorie intake and promote optimal growth and development.
Endocrine Dysfunction (Diabetes):

Insulin: For individuals with CF-related diabetes, insulin therapy is used to manage blood sugar levels. Regular monitoring of blood glucose and close collaboration with an endocrinologist or diabetes specialist are necessary.

Question 46

Can you provide information about new treatments for CF, particularly gene therapy?

Answer 46

Gene therapy has shown promising advancements in the treatment of CF. One notable gene therapy treatment for CF is Kaftrio, which is a triple therapy. It combines a “potentiator” and a “corrector” to address the production and function of the CFTR protein.
The “potentiator” component of Kaftrio helps improve the function of the defective CFTR protein, while the “corrector” component assists in correcting the production and processing of the CFTR protein. This combination therapy aims to enhance the overall function of the CFTR protein, which is crucial for proper chloride ion transport in the cells.

Benefits of Kaftrio and other similar gene therapies for CF may include improved symptoms, increased lung function, and enhanced survival rates. These therapies target the underlying cause of CF by addressing the genetic mutation responsible for the defective CFTR protein.