Cystic fibrosis (CF) affects one in 2,500 newborns and has a UK prevalence of 8,000.
It is the most common inherited condition in white populations, and is increasingly recognised in non-white populations.
CF is an autosomal recessive disorder caused by a mutation at the CF transmembrane conductance regulator gene that affects various cellular activities. These include transport of sodium ions across the respiratory epithelium, pancreatic enzyme secretion and the surface properties of glycoproteins.
The altered sodium metabolism in patients with CF causes increased viscosity of mucus in the respiratory tract, GI tract, pancreas, sweat glands and other exocrine tissues.
CF can present at any age and the presentation varies according to age. In high risk families, the diagnosis may be suspected antenatally stage on the basis of chorionic villous sampling, amniocentesis or ultrasound.
At the neonatal stage, 10 per cent of CF patients may have meconium ileus causing bowel obstruction with possible peritonitis. Less common presentations include gut atresia, obstructive jaundice or fat-soluble vitamin deficiency disorders such as haemolytic anaemia.
In infants and young children the chief presentation is recurrent respiratory symptoms. In addition, 80-95 per cent have pancreatic insufficiency leading to failure to thrive, diarrhoea, abdominal distension and steatorrhoea. Rectal prolapse, electrolyte disturbance, oedema or hypoproteinaemia can also occur.
Recurrent respiratory symptoms also predominate in older children and adults. In this age group pulmonary infection with atypical mycobacteria may be the first indicator of CF. Other presentations include sinusitis, nasal polyps or male infertility due to a bilateral absence of vas deferens.
The GP's role is to identify patients who present with clinical features of CF and refer them on for investigation.
The sweat test remains the gold standard. A chloride level >60mmol/l is diagnostic, 40-60mmol/l is an intermediate result but is more likely to be diagnostic in infants, and <40mmol/l is normal.
Modern wrist-band sweat measuring devices function with very small amounts of sweat and do not have to be worn for long periods of time. If the test is equivocal, other tests are available in some UK centres, such as the nasal potential difference to assess sodium membrane transport.
Pancreatic insufficiency is usually confirmed at the neonatal stage by demonstrating a low level of stool elastase, the presence of un-split fat globules in stool or by stool collection for faecal fat.
Patients fare best in a shared-care arrangement, with primary care co-ordinating nutritional, social and psychological support, while specialist multidisciplinary input is provided by a number of dedicated centres.
The aim of treating early respiratory disease is to promote airway clearance using physiotherapy, mucolytic agents such as dornase alpha, and hypertonic saline.
Prophylactic antibiotics such as flucloxacillin or co-amoxiclav are helpful in the short to medium term, but their effects on long-term survival are unknown.
Infective exacerbations should be treated with antibiotics to cover Haemophilus influenzae and Staphylococcus aureus. Pseudomonas aeruginosa is most commonly found in patients with nasal polyps or sinusitis. When present, ciprofloxacin should be given in the early stages and tobramycin or colistimethate sodium in more chronic disease.
Antibiotics may be given orally, intravenously or via high-flow nebulisers, depending on the patient, the infecting organism and the degree of severity of the infection.
Persistent wheeze may require short-acting bronchodilators and inhaled or oral steroids. Long-term prednisolone for up to two years on alternate days may be beneficial for patients with pseudomonas colonisation. Haemoptysis may be helped by aprotinin or vasopressin analogues, but significant persistent bleeding may require bronchial artery embolisation.
Pneumothorax requires chest drainage, with pleurodesis kept as a last resort as this can affect the patient's suitability for transplant.
Pancreatic insufficiency requires supplementation with pancreatic enzymes and the fat-soluble vitamins A, D, E and K. Patients may also benefit from an alkaline gastric environment created by a PPI or H2 blocker.
Dietary advice should be given and CF patients should have a high-calorie diet. A high fibre and fluid intake is beneficial for patients with constipation. Enteral feeding is sometimes necessary for patients unable to maintain their weight.
Although 32 per cent of CF patients develop diabetes by the age of 25, most are well controlled on insulin, and complications are rare.
Rectal prolapse often resolves with pancreatic enzymes but surgery may be required.
Surgery may also be necessary for meconium ileus, volvulus and intestinal obstruction.
By adulthood, 30 per cent of patients develop liver disease. Ursodeoxycholic acid and taurine are sometimes given to promote bile flow, although the evidence base for long-term benefits is small. Liver transplant may be required in severe cases.
Prognosis and screening
Most male patients with CF have obstructive azoospermia. IVF with aspirated semen has been successful. Women with CF have normal fertility, but need genetic counselling.
The UK national CF screening programme uses the Guthrie blood spot test to detect raised concentrations of immunoreactive trypsinogen. Positive samples are tested for gene mutations and patients referred for sweat testing. Siblings of identified patients should be screened, and asymptomatic adult relatives may wish to be screened for carrier status.
Early identification results in better nutritional support, and 80 per cent of children now survive into adulthood. CF is still a life-limiting disease, although improved care is increasing the length of survival. The UK Cystic Fibrosis survey predicts a survival age of over 50 for patients born in the year 2000.
Psychological issues should not be forgotten. Ongoing morbidity and its treatment is disruptive of ordinary life, and the support of a clinical psychologist can help with coping strategies.
Dr Knott is a GP in Enfield
- 3-11 May is cystic fibrosis fund-raising week. For more information go to www.cftrust.org.uk
- CF is an autosomal recessive, multi-system disorder that affects 1 in 2,500 newborns.
- The presentation is age-specific but normally involves respiratory or GI systems.
- Respiratory management should promote airways clearance and reduce the recurrence of infections.
- GI management should maintain nutritional status and treat pancreatic insufficiency.
- The prognosis has improved with screening and proactive management of early disease.
- Davies J, Alton E, Bush A. Cystic fibrosis. BMJ 2007; 335: 1,255-9.
- Ratjen F, Doring G. Cystic fibrosis. Lancet 2003; 36: 681-9.