Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive genetic condition affecting mucus glands. It is caused by a genetic mutation of the cystic fibrosis transmembrane conductance regulatory gene on chromosome 7. There are many variants of this mutation, the most common is the delta-F508 mutation. This gene codes for cellular channels, particularly a type of chloride channel. Around 1 in 25 are carriers of the mutation and 1 in 2500 children have CF.

The key consequences of the cystic fibrosis mutation are:

  • Thick pancreatic and biliary secretions that cause blockage of the ducts, resulting in a lack of digestive enzymes such as pancreatic lipase in the digestive tract
  • Low volume thick airway secretions that reduce airway clearance, resulting in bacterial colonisation and susceptibility to airway infections
  • Congenital bilateral absence of the vas deferens in males. Patients generally have healthy sperm, but the sperm have no way of getting from the testes to the ejaculate, resulting in male infertility

TOM TIP: Cystic fibrosis is a common exam topic and is a favourite of examiners for testing your knowledge of genetic inheritance. Remember that cystic fibrosis is autosomal recessive. A popular scenario is: both parents are healthy, one sibling has cystic fibrosis and a second child does not have the disease, what is the likelihood of the second child being a carrier? We know the child doesn’t have the condition, so the answer is two in three.

 

Presentation

Cystic fibrosis is screened for at birth with the newborn bloodspot test.

Meconium ileus is often the first sign of cystic fibrosis. The first stool that a baby passes is called meconium. This is usually black and should be passed within 24 hours of birth. In about 20% of babies with CF, the meconium is thick and sticky, causing it to get stuck and obstruct the bowel. This is called meconium ileus, and is practically pathognomonic for cystic fibrosis. This presents as not passing meconium within 24 hours, abdominal distention and vomiting.

If cystic fibrosis is not diagnosed shortly after birth it can present later in childhood with typical signs and symptoms, recurrent lower respiratory tract infections, failure to thrive or pancreatitis.

 

Symptoms

  • Chronic cough
  • Thick sputum production
  • Recurrent respiratory tract infections
  • Loose, greasy stools (steatorrhoea) due to a lack of fat digesting lipase enzymes
  • Abdominal pain and bloating
  • Parents may report the child tastes particularly salty when they kiss them, due to the concentrated salt in the sweat
  • Poor weight and height gain (failure to thrive)

 

Signs

  • Low weight or height on growth charts
  • Nasal polyps
  • Finger clubbing
  • Crackles and wheezes on auscultation
  • Abdominal distention

 

Causes of Clubbing in Children

  • Hereditary clubbing
  • Cyanotic heart disease
  • Infective endocarditis
  • Cystic fibrosis
  • Tuberculosis
  • Inflammatory bowel disease
  • Liver cirrhosis

 

Diagnosis

There are three key methods for establishing a diagnosis that you should remember for your exams:

  • Newborn blood spot testing is performed on all children shortly after birth and picks up most cases
  • The sweat test is the gold standard for diagnosis
  • Genetic testing for CFTR gene can be performed during pregnancy by amniocentesis or chorionic villous sampling, or as a blood test after birth

 

Sweat Test

The sweat test is the key investigation to remember for cystic fibrosis. It is the gold standard for confirming the diagnosis. A patch of skin is chosen for the test, typically on the arm or leg. Pilocarpine is applied to the skin on this patch. Electrodes are placed either side of the patch and a small current is passed between the electrodes. This causes the skin to sweat. The sweat is absorbed with lab issued gauze or filter paper and sent to the lab for testing for the chloride concentration. The diagnostic chloride concentration for cystic fibrosis is more than 60mmol/l.

 

Microbial Colonisers

Patients with cystic fibrosis struggle to clear the secretions in their airways. This creates a perfect environment with plenty of moisture and oxygen for colonies of bacteria to live and replicate. Examples of common colonisers are:

  • Staphylococcus aureus
  • Haemophilus influenza
  • Klebsiella pneumoniae
  • Escherichia coli 
  • Burkhodheria cepacia
  • Pseudomonas aeruginosa

TOM TIP: The key colonisers to remember for your exams are staph aureus and pseudomonas. Patients with cystic fibrosis take long term prophylactic flucloxacillin to prevent staph aureus infection. Pseudomonas should be remembered as a particularly troublesome coloniser that is hard to treat and worsens the prognosis of patients with cystic fibrosis.

 

Pseudomonas Aeruginosa

Once patients become colonised with pseudomonas, it can be very difficult to get rid of. Often, these bacteria can become resistant to multiple antibiotics. Colonisation with pseudomonas leads to a significant increase in morbidity and mortality in patients with CF. In the past there were gatherings and social events organised for children with cystic fibrosis to meet up and share their experiences, however this was stopped due to the risk of spreading pseudomonas. The general advice is now to avoid contact with other children with cystic fibrosis. Cystic fibrosis clinics have separate clinic rooms for children with pseudomonas to minimise the risk of transmission.

Pseudomonas colonisation can be treated with long term nebulised antibiotics such as tobramycin. Oral ciprofloxacin is also used.

 

Management

Cystic fibrosis will be managed by the specialist MDT. There are many aspects to management:

  • Chest physiotherapy several times a day is essential to clear mucus and reduce the risk of infection and colonisation
  • Exercise improves respiratory function and reserve, and helps clear sputum
  • High calorie diet is required for malabsorption, increased respiratory effort, coughing, infections and physiotherapy
  • CREON tablets to digest fats in patients with pancreatic insufficiency (these replace the missing lipase enzymes)
  • Prophylactic flucloxacillin tablets to reduce the risk of bacterial infections (particularly staph aureus)
  • Treat chest infections when they occur
  • Bronchodilators such as salbutamol inhalers can help treat bronchoconstriction
  • Nebulised DNase (dornase alfa) is an enzyme that can break down DNA material in respiratory secretions, making secretions less viscous and easier to clear
  • Nebulised hypertonic saline
  • Vaccinations including pneumococcal, influenza and varicella

 

Other Treatment Options

  • Lung transplantation is an option in end stage respiratory failure
  • Liver transplant in liver failure
  • Fertility treatment involving testicular sperm extraction for infertile males
  • Genetic counselling

 

Monitoring

Patients with cystic fibrosis are managed and followed up in specialist clinics, typically every 6 months. They require regular monitoring of their sputum for colonisation of bacteria like pseudomonas. They also need monitoring and screening for diabetes, osteoporosis, vitamin D deficiency and liver failure.

 

Prognosis

Prognosis depends on multiple factors, including severity of symptoms, type of genetic mutation, adherence to treatment, frequency of infection and lifestyle. Life expectancy is improving and currently the cystic fibrosis trust gives a median life expectancy of 47 years.

  • 90% of patients with CF develop pancreatic insufficiency
  • 50% of adults with CF develop cystic fibrosis-related diabetes and require treatment with insulin
  • 30% of adults with CF develop liver disease
  • Most males are infertile due to absent vas deferens

 

Last updated August 2019
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