CF

Question 1

define

Answer 1

autosomal recessive disorder causing increased viscosity of secretions (e.g. lungs and pancreas).

It is due to a defect in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which codes a cAMP-regulated chloride channel

In the UK 80% of CF cases are due to delta F508 on the long arm of chromosome 7. Cystic fibrosis affects 1 per 2500 births, and the carrier rate is c. 1 in 25

Question 2

Organisms which may colonise CF patients

Answer 2

• Staphylococcus aureus
• Pseudomonas aeruginosa
• Burkholderia cepacia*
• Aspergillus

Question 3

s/s

Answer 3

Presenting features

• neonatal period (around 20%): meconium ileus, less commonly prolonged jaundice
• recurrent chest infections (40%)
• malabsorption (30%): steatorrhoea, failure to thrive
• other features (10%): liver disease

Other features of cystic fibrosis

🍒 Resp manifestations include:

• bronchiectasis with progressive productive cough and green/brown sputum - multiple chest infections
• pneumothorax may occur
• Aspergillus fumigatus and allergic bronchopulmonary aspergillosis in up to 20%.
• colonisation of the lungs by pseudomonas, which is often a difficult problem
• nasal polyposis
• eventually pulmonary fibrosis may lead to death from cor pulmonale or ventilatory failure

🍒 GI manifestations include:

• pancreatic insufficiency leading to malabsorption and failure to thrive.
• gynaecomastia and other signs of chronic liver disease, for example, hepatosplenomegaly
• liver cirrhosis, portal hypertension, hypersplenism - which may develop because of intrahepatic bile duct obstruction caused by abnormal inspissated bile
• distal ileus obstruction syndrome - meconium ileus equivalent
• rectal prolapse - due to bulky stools
• biliary stricture
• gallstones, cholecystitis
• intussusception
• acute pancreatitis

🍒 cardiac problems:

Principally, cor pulmonale, which occurs secondary to pulmonary fibrosis and pulmonary hypertension.

Question 4

ix of CF

Answer 4

1. sputum culture
2. skin test for aspergillus as 20% develop allergic bronchopulmonary aspergillosis
3. pulmonary function tests:
   
   • there may be an obstructive defect causing a reduction in FEV1 and VC
   • the FEV1/VC ratio is reduced
4. in severe cases arterial blood gas sampling shows chronic hypoxia and hypercapnia
5. glucose tolerance test
6. malabsorption screen
7. chest radiography
   
   • may be normal in the early stages of the disease
   • as the disease progresses, bilateral, irregular, fine, blotchy shadowing appears in the middle and upper zones
   • more advanced disease yields the radiological features of bronchiectasis, with:
   • thickened bronchial walls
   • cystic shadows with fluid levels

Question 5

Management of cystic fibrosis

Answer 5

nvolves a multidisciplinary approach

The underlying principles of management of cystic fibrosis are:

1. optimisation of physical and psychological growth
2. delaying the progress of the lung disorder
3. making the lifestyle of the patient and their family as normal as possible

Key points

1. regular (at least twice daily) chest physiotherapy and postural drainage. Parents are usually taught to do this. Deep breathing exercises are also useful
2. high calorie diet, including high fat intake*
3. vitamin supplementation
4. pancreatic enzyme supplements taken with meals
5. antibiotic treatment can be prophylactic and resposive.

• often lifelong to protect against Staph. aureus, the commonest childhood pathogen, Haemophilus inflenzae and Pseudomonas aeruginosa
• antibiotics may be intravenous, using a Port-a-Cath, or they may be nebulised and inhaled
• Pseudomonas becomes a major pathogen with increasing age
• Pseudomonas cepacia colonisation may be associated with accelerated lung disease
• Burkholderia cepacia complex (1)for people with cystic fibrosis who develop a new Burkholderia cepacia complex infection (that is, recent respiratory sample cultures showed no Burkholderia cepacia infection):
• whether they are clinically well or not, give antibiotic eradication therapy using a combination of intravenous antibiotics
• seek specialist microbiological advice on the choice of antibiotics to use.

6. immunomodulatory agents

• if deteriorating lung function or repeated pulmonary exacerbations, offer long-term treatment with azithromycin at an immunomodulatory dose
• if continued deterioration in lung function, or continuing pulmonary exacerbations while receiving long-term treatment with azithromycin, stop azithromycin and consider oral corticosteroids
• do not offer inhaled corticosteroids as an immunomodulatory treatment for cystic fibrosis per se

7. bronchodilators and steroids (oral or inhaled) may be beneficial in patients with allergic bronchopulmonary aspergillosis
8. mucolytics (DNA-ase) improve mucus expectoration
9. mannitol dry powder for inhalation is recommended as an option for treating cystic fibrosis in adults (2)
10. exercise - anecdotal evidence that vigorous aerobic exercise slows lung deterioration; it is said to improve bronchial clearance
11. NIV [non invasive mechanical iventilation = option in end stage disease
12. heart-lung transplantation is a final possibility [5 yr survical = 55%]

*this is now the standard recommendation - previously high calorie, low-fat diets have been recommended to reduce the amount of steatorrhoea

Question 6

complications

Answer 6

• recurrent chest infections
• bronchiectasis esp hemophilus, staphlococcus, pseudomonas
• malabsorption, meconium ileus, intussuception, rectal prolapse
• DMtype 1- 30% by late teens
• male infertility [female fertile but conception may be hard]
• gallstones

Question 7

prognosis

Answer 7

life expectancy = in 3rd decade, but slowly improving

those w/ pancreatic insufficiency and those colonised w/ pseudemonas = poorer prog

gene replacement therapy may be available in future!