Cystic fibrosis

Cystic fibrosis (CF) is an inherited condition that typically presents in early childhood and worsens over time, with increasing damage to the lungs and digestive system. Milder forms of the condition may not present until later in childhood or even into adulthood. Although life expectancy is reduced, with around half of individuals currently living beyond the age of 40, affected individuals who are being born now are likely to live longer than this.

Clinical features of CF include:

• Respiratory symptoms:
  • persistent productive cough with thick mucus;
  • wheeze;
  • recurrent lung infections leading to bronchiectasis;
  • haemoptysis;
  • sinusitis;
  • nasal polyps; and
  • reduced exercise tolerance.
• Gastrointestinal symptoms:
  • meconium ileus in neonates (presenting as bowel obstruction);
  • echogenic bowel observed in the prenatal period;
  • foul-smelling, greasy stools;
  • diarrhoea and/or constipation;
  • difficulty in gaining weight and poor growth;
  • diabetes;
  • liver disease;
  • intestinal obstruction; and
  • rectal prolapse.
• Reproductive symptoms:
  • missing or blocked vas deferens causes infertility for most men; and
  • women may have reduced fertility, while pregnancy can worsen disease progression.

CF is caused by pathogenic variants in both copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

There are many different pathogenic variants in the CFTR gene. Some are common (such as delta F508) and some are rare. Some result in severe disease and some in a milder presentation.

Most new diagnoses of CF in the UK are made through the newborn blood spot (heel prick) test, which includes analysis of immunoreactive trypsinogen (IRT). If IRT levels are above a set cut-off point, genomic testing for up to 100 known common variants in the CFTR gene is conducted.

This testing approach is generally effective; however, occasionally cases are missed, with milder presentations involving rare variants more likely to be missed. Errors at clinical, laboratory or administrative levels are also possible.

It is important to consider the diagnosis of CF in children born outside the UK in countries where newborn screening is not offered.

For information about testing, see Presentation: Clinical suspicion of cystic fibrosis.

CF is an autosomal recessive condition. The parents of most affected individuals are carriers for the condition and therefore have a 25% (one-in-four) chance of having an affected child in each subsequent pregnancy.

Unaffected siblings and other close relatives have a high chance of being carriers. If a carrier has children with another carrier, they have a one-in-four chance of having an affected child. As around 1 in 25 people with European ancestry are carriers of a CF variant (it is lower in other ethnic groups, but still present), there is a small but significant chance of this occurring. Siblings and close relatives should therefore be offered the opportunity to have genomic counselling and testing at an appropriate age to inform their own reproductive choices.

Management of children with CF is complex and should be delivered via a multidisciplinary team. NICE guidelines are available.

Although there is, to date, no definitive cure for CF, there are many approved treatments and a wealth of research and clinical trials. A comprehensive overview of clinical trials in CFTR modulator therapies is available.

The Cystic Fibrosis Foundation provides useful documents for health professionals, including clinical guidelines, research pipelines and details of clinical trials. For more resources, see below.

For clinicians

• ClinicalTrials.gov
• Cystic Fibrosis Foundation: For medical professionals
• Genomics England: NHS Genomic Medicine Service (GMS) Signed Off Panels Resource
• National Organization for Rare Disorders: Cystic fibrosis
• NHS England: National Genomic Test Directory
• NICE: Guidelines for the diagnosis and management of cystic fibrosis
• UpToDate: Cystic fibrosis: Genetics and pathogenesis

For patients

• British Lung Foundation: Cystic fibrosis
• Cystic Fibrosis Foundation
• Cystic Fibrosis Trust