Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive genetic condition affecting the mucus glands. The key consequences of cystic fibrosis are:

  • Thick bile duct and pancreatic secretions
  • Thick airway secretions
  • Congenital bilateral absence of the vas deferens (males)

 

Thick and sticky secretions can block the pancreatic and bile ducts, preventing digestive enzymes (e.g., pancreatic lipase) from entering the digestive tract. Chronic obstruction can lead to liver disease, pancreatitis and diabetes.

Thick and sticky airway secretions reduce airway clearance, resulting in a chronic cough, bacterial colonisation and recurrent infections.

Congenital absence of the vas deferens causes male infertility. Patients generally have healthy sperm, but the sperm have no way of getting from the testes to the ejaculate. Surgical sperm retrieval, followed by in-vitro fertilisation, can be used to treat male infertility.

There is variation depending on the individual:

  • 85% of patients with CF develop pancreatic insufficiency
  • 30-50% of adults with CF develop cystic fibrosis diabetes
  • 30% of adults with CF develop liver disease
  • 95% of males with CF are infertile due to absence of the vas deferens

 

Genetics

Cystic fibrosis is caused by a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7. There are many variants of this mutation. The most common is the delta-F508 mutation. The gene codes for a chloride ion channel in epithelial cells, notably in the lungs, pancreas, bile ducts and bowel.

Cystic fibrosis is an autosomal recessive condition, meaning that two abnormal copies are required for someone to have the disease. Around 1 in 2500 children have cystic fibrosis, and 1 in 25 are carriers of the mutation.

TOM TIP: A popular exam scenario involves two healthy parents who have one child with cystic fibrosis and one child without cystic fibrosis. The question asks the probability that the second child is a carrier. Both parents must be carriers for the first child to have the disease. The second child has a 1 in 3 chance of having two normal copies, and a 2 in 3 chance of having one abnormal copy and one normal copy. Therefore, the answer is 2/3.

 

Presentation

Meconium ileus is often the first sign of cystic fibrosis. The first stool that a neonate passes is called meconium. This is usually dark green and passes 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 almost always caused by cystic fibrosis. It presents with not passing a stool within 24 hours of birth, abdominal distention and vomiting.

Cystic fibrosis can present later in childhood with:

  • Recurrent lower respiratory tract infections
  • Failure to thrive
  • Pancreatitis

 

Clinical Features

Children with cystic fibrosis often have ongoing:

  • 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
  • Poor weight gain
  • Reduced height

 

Parents may report that the child tastes salty when they kiss them due to the concentration of sweat.

Signs on examination include:

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

 

TOM TIP: Remember the three causes of clubbing in children: cyanotic heart disease, inflammatory bowel disease and cystic fibrosis.

 

Diagnosis

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

The sweat test is the key diagnostic test when cystic fibrosis is suspected. Pilocarpine is applied to a patch of skin on an arm or leg. Electrodes are placed on either side of the patch, and a small current is applied, causing the skin to sweat. The sweat is absorbed with lab-issued gauze or filter paper. Chloride is normally reabsorbed from sweat through the CFTR. In cystic fibrosis, chloride reabsorption from sweat is impaired due to the malfunctioning CFTR, leading to a higher chloride concentration. A chloride concentration of more than 60mmol/l indicates a diagnosis.

Genetic testing for the CFTR gene can confirm the genetic mutation. Relatives may be offered testing for carrier status.

 

Microbial Colonisers

The thick, sticky airway secretions create an environment with plenty of moisture and oxygen for bacteria to live and grow. Common colonisers include:

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

 

TOM TIP: The key colonisers to remember in CF are Staphylococcus aureus and Pseudomonas aeruginosa. Patients take long term prophylactic flucloxacillin to prevent staph aureus infection.

 

Pseudomonas Aeruginosa

Colonisation with Pseudomonas can be difficult to treat. It increases the morbidity and mortality in patients with CF.

Around 25% of CF patients are colonised with Pseudomonas. Patients are advised to avoid social contact with other children with cystic fibrosis and clinics have separate areas for colonised children to minimise the risk of transmission.

Pseudomonas colonisation may be treated with:

  • Nebulised antibiotics (e.g., colistimethate or tobramycin)
  • Oral ciprofloxacin

 

Management

Cystic fibrosis is managed by a specialist multidisciplinary team, which includes follow-up and complication monitoring.

CFTR modulator therapies (e.g., Kaftrio, Symkevi and Orkambi) are combination drugs that include ivacaftor. They directly interact with the cystic fibrosis transmembrane conductance regulator (CFTR) protein, improving its function. They are available for patients who meet specific criteria and can improve lung and pancreatic function.

Standard treatment includes:

  • Chest physiotherapy several times a day 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
  • Pancreatic enzyme replacement therapy (e.g., CREON tablets) to digest fats in pancreatic insufficiency
  • Prophylactic flucloxacillin to reduce the risk of Staphylococcus aureus colonisation and infection
  • Long-term azithromycin for recurrent infections
  • Bronchodilators (e.g., salbutamol) to treat bronchoconstriction
  • Nebulised DNase (dornase alfa) breaks down DNA material in respiratory secretions, making them less viscous
  • Nebulised hypertonic saline to make secretions less viscous
  • Inhaled mannitol dry powder to make secretions less viscous
  • Nasal steroids for nasal polyps
  • Vaccinations, including influenza and covid

 

Other treatment options include:

  • Home oxygen (if necessary)
  • Insulin for cystic fibrosis diabetes
  • Lung transplantation in end-stage respiratory failure
  • Liver transplant in end-stage liver failure
  • Fertility treatment involving testicular sperm extraction for infertile males
  • Genetic counselling

 

Prognosis

The prognosis depends on many factors, including symptom severity, genetic mutation, treatment adherence, infection frequency and lifestyle. Life expectancy is improving, and in their 2023 Annual Data Report, the Cystic Fibrosis Trust predicts that half of those born at the time would live to 64 years.

 

Last updated February 2025

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