12. tbl. 94. árg. 2008

Fræðigrein

Cystic Fibrosis - Review

Slímseigjusjúkdómur (cystic fibrosis): meingerð, greining og meðferð - Yfirlitsgrein

The purpose of this paper is to give a brief overview of cystic fibrosis; its pathogenesis, diagnosis, treatment and prognosis. Cystic fibrosis is an autosomal recessive disorder, which is caused by a mutation in the CFTR protein, a chloride channel in epithelial cell membranes. More than 1500 mutations are known. The incidence is 1/2.000-3.000 in nations of European origin. The CFTR mutation influences the secretion and absorption by epithelium in various organs. The consequences are different depending on the organ, but there is a global tendency for obstruction of secretory glands. The primary organs affected are the respiratory tract, pancreas, gastrointestinal tract and sweat glands. The disease is most often diagnosed during the first months of life, with a common presentation of salty tasting sweat, failure to thrive and diverse faecal problems. Possible diagnostic tools are sweat test and DNA testing. Respiratory symptoms cause most morbidity, with chronic infections and an exaggerated inflammatory response. Abnormal water and electrolyte composition leads to thicker respiratory secretions compared to that of healthy individuals. The interaction of pathogens with the epithelium causes S.aureus, and later P.aeuruginosa, to transform into a mucoid form which is much more difficult to eradicate with antibiotics, making them a significant part of the disease burden of cystic fibrosis. The main respiratory medications are antibiotics, bronchodilators, mucolytic agents and anti-inflammatory agents. 90% of cystic fibrosis patients have pancreas insufficiency which is treated with pancreas enzymes. A good nutritional status is a necessary basis for any further treatment. The prognosis of cystic fibrosis patients has improved greatly over the last few decades in parallel with increased knowledge, and the average survival is currently 37 years in the United States.

Respiratory system	Repeated pneumonia*
	Chronic bronchitis*
	Staphylococcal infection in the respiratory tract*
	Longstanding cough*
	Pansinusitis
	P. aeruginosa in bronchial lavage fluid
	Nasal polyps
Gastrointestinal system	Abundant, foul smelling or fatty stools*
	Failure to thrive*
	Meconium ileus*
	Intussusception*
	Distal intestinal obstructive syndrome
	Rectal prolapse
	Unexplained cirrhosis, gallstones or pancreatitis before age 30
	Symptoms because of deficiency of lipophilic vitamins (A,D,E,K)
Other symptoms	Salty taste of sweat*
	Hyponatremia or metabolic alkalosis in children
	Clubbing
	Infertility, defect in seminal tract
	Anasarca

Table I: The symptoms of cystic fibrosis, catagorized by organ systems. (*) Initial symptoms (10). For further information, see main text.

Treatment group

Action

Indications

Other information

Antibiotics

Attacks pathogens.

Acute exacerbations, bacteria in sputum.

Additional information in main text.

b-adrenergic agonists

Attack obstruction in airways, but it exists because of the clotting of airways with mucus and thickening of the bronchial wall because of inflammation.

Used in most adult patients, especially if asthma like symptoms occur. Has little effect on severe disease. Also used in acute exacerbations.

Few randomised studies have been done regarding effect of use, but nonetheless these drugs are widely used. Well tolerated.

Drugs that increase secretion of airways:

ØHypertonic saline (aerosol)

ØDNase (Pulmozyme)

ØN-acetyl-cystein (Mucomyst)

ØIncreases mucus cleaning in airways, increases pulmonary function, decreases exacerbations.

ØSubdivides DNA to smaller fragments, decreases viscosity of the mucus. Increases pulmonary function.

ØDecreases mucus viscosity in vitro, probably by breaking sulphide-junctions.

ØNot entirely clear when to give, is most likely effective for all patients.

ØPatients with daily cough and sputum production and at least mild obstruction.

ØNot clear when to give, does not seem to have much effect.

ØInexpensive drug.

ØExpensive. Given once a day in aerosol form.

ØResearches have not proven effect in vivo.

Anti-inflammatory drugs

Decrease inflammation in airways

Asthma symptoms. The use of Macrolides can be effective in chronic P.aeruginosa infection.

Additional information in main text.

Physiotherapy

Helps to cough up mucus.

Important treatment in all patients who produce sputum daily.

Many different methods, e.g. banking, respiratory patterns and vests.

Oxygen

Used in respiratory failure to inhibit pulmonary hypertension and cor pulmonale.

Severe hypoxia.

No good data on efficacy.

Table II: Possible treatments in cystic fibrosis (4,6,15,23,24,25,26).

Lung transplant

Increases survival.

Steadily increasing respiratory failure, decreasing function, major lung complications or increasing antibiotic resistance.

Careful evaluation of benefits needs to be in place before treatment decision is made.