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Cystic fibrosis 

Cystic fibrosis

Cystic fibrosis

Andrew Bush

and Caroline Elston



Infection—increased recognition of the importance of lung infection with Mycobacterium abscessus.

Future prospects—new animal models that more precisely replicate human disease; the highly efficacious use of Ivacaftor in patients with the G551D mutation, who comprise 4–5% of patients with CF.

Updated on 28 Aug 2014. The previous version of this content can be found here.
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date: 28 April 2017

Cystic Fibrosis (CF) is a recessively inherited disease caused by mutations in the cystic fibrosis gene, located on the long arm of chromosome 7, which codes for a membrane protein—the cystic fibrosis transmembrane regulator protein (CFTR)—that is a chloride channel. Around 1300 CF mutations have been identified, with the Δ‎F508 mutation being the most common (70% of CF chromosomes in the European population). Birth incidence varies with country of origin from 1 in 2000 to 1 in 100 000.

Pathophysiology—the mutant CFTR fails to transport chloride ions normally, and there is secondary impairment of sodium, bicarbonate, and water transport. This leads to dehydration of pancreatic secretions, eventually leading to pancreatic failure, and in the lungs to increased fluid absorption from the airway lumen and reduction in the depth of the film of airway surface liquid (the ‘low volume hypothesis’), with impairment of ciliary function, mucus stasis, and thus chronic infection and inflammation.

Clinical features—most cases of CF are diagnosed in early childhood by newborn screening, or, with the classical clinical picture of pancreatic insufficiency and suppurative lung disease, but patients with milder genetic mutations may present in late childhood or adulthood. Other pulmonary manifestations include haemoptysis, pneumothorax, allergic bronchopulmonary aspergillosis (ABPA), and atypical mycobacterial infection. Patients presenting in adult life are often clinically pancreatic sufficient, or they present with other conditions that are also associated with CF gene mutations, e.g. azoospermia, idiopathic pancreatitis.

Diagnosis—this is usually established by the sweat test (pilocarpine iontopheresis or macroduct collection) revealing a high sweat chloride concentration, although increasingly the diagnosis is likely to be made by newborn screening (heel prick blood samples tested for immunoreactive trypsin and by PCR for common CF mutations).

Prognosis—pulmonary infection and inflammation account for most CF-associated morbidity and mortality. The lungs become transiently infected in early childhood and ultimately chronically infected, typically with Staphylococcus aureus and Haemophilus influenzae, and subsequently with Pseudomonas aeruginosa, which is associated with a worse prognosis. Chronic infection and inflammation lead to bronchiectasis, progressive airflow obstruction, and ultimately death from respiratory failure, although outcome has improved dramatically over the past 20 years such that estimated survival for a child born with CF in the late 1990s is 40 to 50 years.

Management of respiratory disease—airway clearance with regular physiotherapy is an integral part of routine management. Antibiotic treatment is initially directed at preventing chronic infection. Prophylactic nebulized antibiotic therapy (colomycin, tobramycin) is beneficial once patients become chronically infected with Pseudomonas. Mucolytic agents are often indicated. Azithromycin, a macrolide antibiotic that appears to modulate inflammation in CF by an ill-understood mechanism, is used increasingly.

Management of other features—(1) Pancreatic insufficiency is associated with malabsorption and requires pancreatic enzyme replacement therapy and a high-energy diet in most patients. (2) Distal intestinal obstruction syndrome—severe constipation sometimes leading to bowel obstruction with faecal material in the distal ileum and associated abdominal pain—is relatively common. (3) Diabetes—this occurs in up to 30% of patients, with the incidence increasing with age; a high-energy diet should be maintained, with insulin doses adjusted accordingly. (4) Liver function—mild abnormalities are common, with disease progression to cirrhosis in around 5% of patients. (5) Fertility—nearly all men with CF are infertile, but most women with CF can conceive normally. (6) Osteoporosis—low bone mineral density is found in 60% of patients.

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