Cystic Fibrosis

Question 1

How is CF inherited?

Answer 1

Autosomal recessive

Inheritance of defective CTFR gene on chromosome 7

Question 2

What is life expectancy?

Answer 2

40s

95% die of respiratory failure

Question 3

What is the fundamental problem in CF?

Answer 3

Defective protein called the CF transmembrane conductance regulator CFTR.
AMP dependent chloride channel found in the membrane of cells.
The gene for CTFR is found on chromosome 7
Various mutations cause various problems - most common is class II - incorrect folding means the channel cannot be trafficked to the membrane.

Question 4

Describe the pathophysiology in CF.

Answer 4

Abnormal ion transport across epithelial cells.
In the airways this leads to reduction in the airway surface liquid layer and consequent impaired ciliary function and retention of mucopurulent secretions.

Chronic endobronchial infection with specific organisms ensues - Pseudomonas aeruginosa ensues

Defective CFTR also causes dysregultaiton of inflammation and defence against infection.

In intestine, thick viscid meconium (dark green substance forming first faeces) is produced leading to meconium ileus.

Pancreatic ducts also become blocked by thick secretions leading to pancreatic enzyme deficiency and malabsorption.

Abnormal function of the sweat glands results in excessive concentration of sodium and chloride in the sweat.

Question 5

Four parts of the body CF affects?

Answer 5

Airway
reduction in the airway surface liquid layer and consequent impaired ciliary function and retention of mucopurulent secretions

Intestines
thick viscid meconium (dark green substance forming first faeces) is produced leading to meconium ileus.

Pancreas
Pancreatic ducts also become blocked by thick secretions leading to pancreatic enzyme deficiency and malabsorption.

Sweat glands
excessive concentration of sodium and chloride in the sweat.

Question 6

What infections are CF susceptible to?

What does this lead to?

Answer 6

Chronic endobronchial infection by
Staph aureus and Haemophilus influenza initially
Subsequently with Pseudomonas aeruginosa, or Burkholderia

Results from mucus in the smaller airways,

This leas to damage fo the bronchial wall, bronchiectasis, and abscess formation.

Question 7

Describe CF screening.

Answer 7

All infants born in UK are screened - immunoreactive trypsinogen is raised in newborn infants with CF and is measured in routing heel-prick blood taken for biochemical screening.
Those samples with a raised IRT are screened for common CF gene mutations.
Infants with 2 mutations have a sweat test to confirm diagnosis

Question 8

How may CF children present? How do infections present in CF children?

Answer 8

Recurrent chest infections:
Wet cough, productive or purulent sputum.
Hyperinflation of chest due to air trapping
Inspiratory crepitations
Expiratory wheeze

Faltering growth
Malabsorption

Finger clubbing in established disease

Question 9

Clinical features of CF in newborn?

Answer 9

Screening diagnosis
Meconium ileus - thickened meconium causes intestinal obstruction - vomiting, abdominal distention and failure to pass meconium in the first few days of life. - Surgery.,

Question 10

Clinical features of CF in infants?

Answer 10

Prolonged neonatal jaundice
Growth faltering
Recurrent chest infections
Malabsorption, steatorrhoea

Question 11

Clinical features of CF in young child?

Answer 11

Bronchiectasis
Rectal prolapse
Nasal polyp
Sinusitis

Question 12

Clinical features of CF in older child and adolescent

Answer 12

Allergic bronchopulmonary aspergillosis
DM
Cirrhosis and portal hypertension
Distal intestinal obstruction
Pneumothorax or recurrent haemoptysis
Sterility in males

Question 13

Why do CF children struggle with growth? How do you show this?

Answer 13

CF have pancreatic exocrine insufficiency (lipase, amylase, protease) resulting in maldigestion and malabsorption.
This leads to faltering growth with frequent large pale and greasy stools (steatorrhoea).

Can be diagnosed by demonstrating low faecal elastase.

Question 14

How is CF diagnosed?

Answer 14

Sweat test
to confirm the concentration of chloride in the sweat is markedly elevated.
Sweating is stimulated by applying a low voltage current to pilocarpine applied to the skin.
The sweat is collected into a special tube.
Confirmation of diagnosis can be made by testing for gene abnormalities in the CFTR protein.

Question 15

Aim of therapy in CF?

Answer 15

Prevent the progression of lung disease and maintain adequate nutrition and growth.

Question 16

How is severity of respiratory disease in CF monitored?

Answer 16

Results spirometry

FEV1 is a clinical indicator of severity and declines with disease progression.

Question 17

Describe respiratory management of CF.

Answer 17

Physiotherapy twice a day aiming to clear airway of secretions.
Parents taught to perform airway clearance at home using chest percussion and postural drainage in young.
Older patients perform controlled deep breathing and use a variety of devices.
Physical exercise is beneficial.

Continuous prophylactic oral abx (Flucloxacillin) with additional rescue oral abx for any increase in symptoms or decline in function.

Persisting symptoms require prompt vigorous IV therapy for 14 days via a PIC (peripherally inserted central) line.
Parents are taught to administer IV abx at home.

Nebulised antipseudomonal abx slow the decline of function due to Pseudomonas.

Neubulised DNase or hypertonic saline maybe helpful to decrease viscosity of sputum.

Azithromycin (macrolide) given regularly decreases exacerbations due to immunomodulatroy effect.

Question 18

In severe CF that requires regular IV therapy what can you do?

Answer 18

Implant a central venous catheter with subcutaneous port

Requires monthly flushing

Question 19

What is the option for end stage CF lung disease.

Answer 19

Bilateral sequential lung transplantation

Question 20

Describe nutritional management in CF? How is pancreatic insufficiency treated? Describe diet.

Answer 20

Dietary status assessed regularly
Pancreatic insufficiency treated with oral enteric-coated pancreatic replacement therapy taken with all meals and snacks.

High calorie diet is essential - 150% of normal.
Overnight feeding via a gastrostomy in used to achieve this.

Fat soluble vitamin supplements ADEK

Question 21

What are complications of CF in teenagers and adults and how are these managed?

Answer 21

Diabetes mellitus
Liver disease with hepatomegaly, abnormal LFTs, or abnormal USS.
Regular ursodeoxycholic acid to improve bile flow may be beneficial.
Liver transplant is successful in CF related liver failure

Distal intestinal obstruction syndrome - viscid mucofaeculent material obstructs bowel - cleared by oral laxatives.

Increasing chest infections with pneumothorax and haemoptysis. Patients segregated and advised not to socialise with other CF to prevent spread of Pseudomonas and Burkholderia.

Males infertile due to absence of vas deferens
Can father children through intracytoplasmic sperm injection.

Psychological repercussions.
- provide psychological and emotional support

Question 22

What is primary ciliary dyskinesia? Clinical features? Diagnosis? Management?

Answer 22

Congenital abnormality in the structure or function of cilia lining respiratory tract.
Leads to impaired mucociliary clearance.

Recurrent infection of upper and lower respiratory tracts which may lead to severe bronchiectasis.

Recurrent productive cough, purulent nasal discharge and chronic ear infections.

50% have dextrocardia and situs inversus (Kartagener syndrome where major organs are in mirror)

Diagnosis is made by examination of structure and function of cilia in nose

Daily physiotherapy to clear secretions
Proactive treatment with abx