Cystic fibrosis

Cystic fibrosis

Cystic fibrosis is the most severe autosomal recessive disease as a result of mutations affecting a gene located on the Ions arm of chromosome 7

which encode for the chloride channel which is essential for the regulation of salt and water movement across the cell membrane.

Mostly affected patients belong to the white young population of northern Europe and America.

PATHOGENESIS

The genetic defect causes an increased sodium chloride content in sweat resulting in much-increased viscosity of secretions that leads to the production of abnormal mucus by exocrine glands. This viscous mucus obstructs glands and ducts which ultimately causes glandular dilatation and damage to the tissue.

In the respiratory tract, inadequate hydration of tracheobronchial epithelium impairs mucociliary function. Ciliary dysfunction and chronic bronchial infection lead to bronchiectasis involving gradually all areas of both lungs. Bronchiectasis usually develops at a young age.

There are also disorders in the gut epithelium, pancreas, and liver causing malabsorption, diabetes, and liver cirrhosis.

Most men with cystic fibrosis are infertile due to the failure of the development of vas deferens.

Early diagnosis can be achieved by neonatal screening and amniocentesis.

CLINICAL FEATURES

Respiratory effects

Recurrent bronchopulmonary infection especially bronchiectasis presenting with cough with sputum decreased exercise tolerance and haemoptysis.

Sinusitis presents as facial pain and purulent nasal discharge.

Clubbing is also present due to the presence of pus in the lung.

Older children may develop nasal polyps.

Spontaneous pneumothorax may occur.

Cor pulmonale and respiratory failure eventually develop.

Gastrointestinal features

Pancreatic dysfunction leads to steatorrhea.

Small intestinal obstruction due to meconium ileus

Cholesterol gallstone

Cirrhosis of liver

There is also an increased incidence of peptic ulceration and G1 malignancy.

Malnutrition and malabsorption

Puberty and skeletal maturity are delayed.

Infertility in males due to failure of development of vas deferens and epididymis.

Females are able to conceive but often develop secondary’ amenorrhea as the disease progresses.

Joint disease and diabetes mellitus also occur.

COMPLICATIONS OF CYSTIC FIBROSIS

Respiratory

Haemoptysis

Spontaneous pneumothorax

Nasal polyps

Cor- pulmonale

Respiratory failure

Gastrointestinal

Intestinal obstruction

Biliary cirrhosis

Cholesterol gallstones

Malabsorption syndrome

Others

Diabetes mellitus

Delayed puberty

Male infertility

Arthropathy

Amyloidosis

Psychosocial problems – Depression

DIAGNOSIS

Sweat test:

Blood DNA analysis for gene defect.

MANAGEMENT

Postural drainage and chest physiotherapy for clearance of lower airway secretions.

Antibiotics: for infection. Common organisms are staph, aureus, H. influenzae,

Inhaled bronchodilators: such as salbutamol (Ventolin).

Inhaled corticosteroids: to reduce inflammation.

Vaccination: for pneumococcal infection and annual influenza vaccination.

Lung transplantation

Genetic screening of family members