Definition of cystic fibrosis

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Cystic fibrosis is a hereditary disease that causes certain glands to produce abnormal secretions, particularly the lungs and the digestive tract. The increased viscosity of the secretions is caused by abnormal ion transport across the epithelial cells of exocrine glands of the respiratory tract and the pancreas. These secretions can cause tissue and organ damage. It is an autosomal recessive disease affecting 1 in 2500 births and, in UK, newborn screening is undertaken via blood spots on the Guthrie card taken at 5 days of age. Other tests such as gene testing and sweat tests can be performed in older children. Cystic fibrosis will affect patients in different ways depending on the extent of the organs involved but about 80-90% will have pancreatic insufficiency and chronic suppurative lung disease. Liver involvement can lead to cirrhosis and obstruction to the vas deferens can result in male infertility. Cystic Fibrosis is the UK's most common life-threatening inherited disease. Non- pharmacological symptom management in cystic fibrosis

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Although drug treatment is important in the management of cystic fibrosis, good nutrition and regular physiotherapy are essential. Aggressive nutritional support can increase survival. Energy requirements in patients with CF may be 30 40% above normal and so a high energy diet is essential to provide this as well as compensating for malabsorption. To achieve this overnight feeding via a gastrostomy may be required. Fat soluble vitamins will also be required if there is pancreatic insufficiency. Vitamins A and D have been shown to be lower in patients with CF and require supplementation. The anti-oxidant properties of vitamin E may ameliorate the deterioration in cell function and is therefore often supplemented. Supplements of vitamin K are usually only required if the patient has significant liver disease. Physiotherapy is an essential part of the management of lung disease. There are various techniques including percussion, forced expiration and passive postural drainage. Coughing can be helped by the use of nebulised hypertonic saline. Patients should be treated twice a day and parents are taught to perform physiotherapy at home. Pharmacological management of cystic fibrosis

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On diagnosis the main concerns are to maximise nutrition and to protect the lungs and in order to achieve this pancreatic enzymes, vitamins and flucloxacillin should be considered. Mechanism of action and side-effects of pancreatin

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Pancreatic enzymes are formulated as pancreatin which is a mixture of lipase, amylase and protease in varying proportions. These enzymes will aid digestion of starch, fat and protein. The dose is adjusted until normal stool frequency and consistency is achieved. It should be given with each meal and extra doses may be required if snacks are taken between meals. However following concerns about the development of large bowel strictures (fibrosing colonopathy) with higher strength pancreatin preparations in children aged between 2 and 13 years the CSM has recommended; -Higher strength preparations (e.g. Pancrease HL and Nutrizym 22) should not be used in children under 16 years of age -The total dose of pancreatic enzyme supplements used in patients with CF should not usually exceed 10,000units of lipase per kg body weight per day. -If a patient on any pancreatin preparation develops new abdominal symptoms the patient should be reviewed to exclude colonic damage. Pancreatin is inactivated by gastric acid and therefore preparations should be taken at the same time as food. Occasionally a proton pump inhibitor or a H2 receptor antagonist may be required to improve fat digestion and absorption. Some enteric coated preparations are designed to deliver a higher enzyme concentration in the duodenum but this is dependent on the capsules being swallowed whole and not chewed. The contents may be mixed with a little soft food if the capsule cannot be swallowed. Pancreatin can irritate the gums and it is important to check that none of the granules are left in contact as they can cause ulceration. If the dose is too high perianal irritation can be problematic and a barrier cream may be required. Other side effects include nausea, vomiting, abdominal discomfort, hypersensitivity and hyperuricaemia and hyperuricosuria. Mechanism of action and side-effects of anti-infective use in cystic fibrosis

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Antibiotics will be required in CF patients for both the treatment of acute infections and the prevention and control of chronic colonisations. Unlike the policy advocated in most patients that antibiotic use should be restricted, the general approach in CF is to treat aggressively, often with higher doses for longer periods compared with non-CF individuals. Secondary bacterial infection can quickly follow viral upper respiratory tract infections so a course of oral antibiotics is often prescribed to minimise the risk. In CF chronic and progressive lower respiratory tract infection may lead to death in early childhood, unless antibiotic treatment is used. Metabolism and clearance of antibiotics is altered in patients with CF and therefore different doses may be required. It is important that doses are checked for the correct indication and

patient population before treatment is commenced. The frequency of treatment may lead to long term problems with adverse effects from some commonly used antibiotics such as gentamicin or tobramycin in which impairment of renal function, or hearing may occur if there is not close monitoring. Hypersensitivity reactions may occur following repeated exposure to the antibiotics. The use of implantable venous access devices allows the administration of intravenous antibiotics in the home by parents. Although admissions to hospital may be unavoidable in many cases, it is important to prevent the cross infection of patients and treating away from the hospital will reduce the risk of acquiring other, and possibly resistant, infections. The main organisms of concern are: Staphylococcus aureus including MRSA Haemophilus Influenzae Pseudomonas aeruginosa The classic sequence is age-related and consists of S. aureus in early infancy, followed by H. influenzae and P. aeruginosa. P. aeruginosa is difficult to eradicate but when it is first isolated nebulised colistin may be given for several months as well as a course of oral treatment to attempt eradication. If there are repeated re-isolations then nebulised colistin may be continued indefinitely. During the last decade, the B. cepacia complex has emerged as a major pathogen in CF. Burkholderia cepacia has become a particular problem because of its multiresistance and the transmissibility of some strains. In approximately one-third of infected patients the organism causes cepacia syndrome, a fulminating pneumonia and septicaemia that can be swiftly fatal. The choice of antibiotic will depend on previous drug history, as well as the likely pathogens and sensitivities. Details of drugs are not given here but BNFC includes doses for patients with cystic fibrosis when these vary from the normal ones. Anti-fungal agents may be required if Allergic bronchopulmonary aspergillosis (ABPA) is diagnosed. ABPA is an IgE and IgG mediated hypersensitivity to A. fumigatus. It is relatively common, occurring in up to 10% of patients. Mechanism of action and side-effects of specific therapies in cystic fibrosis

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Recombinant human DNase (Dornase) digests DNA released from neutrophils within the airway lumen. It decreases the viscosity of the sputum and helps with clearance of mucus. It is administered by nebulisers and individual centres will have their own criteria for starting therapy but it is only indicated for the CF patients, over 5 years old, with a forced vital capacity (FVC) of greater than 40% of predicted as its efficacy has not been demonstrated in patients with FVC less than 40%. It should be tried for several months and then reassessed to see if there is any improvement in FVC. It should be given at least 1 hour before physiotherapy as the most benefit is seen 1-3 hours after the dose. Voice alteration and rash are occasional side effects.

Azithromycin has been shown to have some anti-inflammatory as well as antibiotic effects and trials have shown that long term azithromycin over 6 months increased lung function. If it has been shown to improve lung function it can be continued long term and in many cases it can be reduced to doses on three days a week. Nausea, abdominal pain and diarrhoea are the most common side effects. Complications of cystic fibrosis

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CF related diabetes is caused by insulin deficiency following progressive deterioration in pancreatic beta-cell function. It is different from type 1 or type 2 diabetes but needs insulin therapy adjusted to ensure a good calorie intake. CF related liver disease can manifest itself in a range of severity from symptomless biochemical changes to cirrhosis and portal hypertension. There is some evidence that ursodeoxycholic acid may prevent the progression to cirrhosis and improve bile flow. It may cause transient diarrhoea but is otherwise well tolerated.