2 Clinical need and practice
2.1 Cystic fibrosis is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It is characterised by abnormal transport of chloride and sodium across transporting epithelia, leading to thick viscous secretions in the lungs, pancreas, liver, intestine and reproductive tract and to an increased salt content in sweat gland secretions. People with cystic fibrosis have problems with their respiratory system and digestion, including prolonged diarrhoea that can affect growth and body mass index. They are prone to lung infections by a range of pathogens including Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa and Burkholderia cepacia. This is thought to be because the thick mucus makes it difficult for the body to clear inhaled bacteria, and because people with cystic fibrosis have an increased airway inflammatory response to pathogens. Chronic inflammation and progressive lung destruction from chronic infection can lead to bronchiectasis, altered pulmonary function and respiratory failure.
2.2 Cystic fibrosis affects over 8500 children and young adults in the UK and has an incidence of 1 in 2500 live births. About 1 in 25 people in the UK of white European origin are carriers of an affected CFTR gene. It is much less common in people of African-Caribbean and Asian origin. Cystic fibrosis is a progressive condition that reduces life expectancy. In 2010, the cystic fibrosis registry recorded 103 deaths in UK patients; the median age at death was 29 years. However, prognosis is improving with the treatments now available and around half of the current cystic fibrosis population are expected to have a life expectancy of over 38 years.
2.3 Management of the pulmonary component of cystic fibrosis includes a range of measures to aid clearance of respiratory secretions and to decrease inflammation and bacterial growth in the respiratory tract, such as chest physiotherapy, inhaled bronchodilators, inhaled mucolytics (such as rhDNase and hypertonic saline) and antibiotic treatment. The aim of treatment is to delay or slow deterioration in lung function, measured by forced expiratory volume in 1 second (FEV1). Ultimately, patients may become eligible for lung transplantation. The care of most patients in the UK is coordinated by a tertiary cystic fibrosis centre with formal shared care with local clinics. Cystic fibrosis treatment can be time-consuming for the patient, with administration of nebulised antibiotics taking up to an hour each day during good health and longer during periods of ill health. The disease also impacts upon carers and needs a considerable commitment of healthcare resources.
2.4 P. aeruginosa is the most frequent cause of lung infection in people with cystic fibrosis; around 38% of UK patients had a chronic pseudomonas infection in 2010. If recurrent intermittent infections are not controlled, chronic infection can develop in which bacterial microenvironments known as biofilms are formed that are difficult for immune cells and antibiotics to penetrate. The length and quality of life of people with cystic fibrosis are thought to be strongly influenced by the degree to which P. aeruginosa can be eradicated; however, chronic P. aeruginosa infection is rarely completely eradicated.
2.5 Management of P. aeruginosa lung infection in cystic fibrosis involves treatment with antibiotics, which may be given in hospital, at home or in a combination of these settings. The aims of antibiotic treatment are three-fold: firstly to eradicate intermittent acute P. aeruginosa lung infections; secondly to suppress P. aeruginosa (with long-term treatment) in patients who have become chronically infected; and thirdly to treat acute exacerbations in patients chronically infected with P. aeruginosa. Treatment also aims to maintain lung function and quality of life. Current treatment options include the use of inhaled antibiotics effective against P. aeruginosa (such as nebulised colistimethate sodium or tobramycin) and oral or intravenous antibiotics to eradicate initial or intermittent P. aeruginosa colonisation or acute exacerbations of chronic infection. Azithromycin may be given in combination with these antibiotics to act on the biofilms.