• Briefly explain what cystic fibrosis is and how dornase alfa acts to solve the problem.

Cystic fibrosis is a genetic defect that can lead to a decrease in secretions in various organs. The most prominent manifestation and problematic symptom is in the airways. The airway has exceptionally thick and sticky mucus secretions which provides an excellent environment for bacterial infections. The repeated infections cause continuous chemotaxis of neutrophils which then leads to deposits of DNA (this occurs during disintegration),which makes the mucus even stickier. The mucus then becomes virtually impossible to clear and a vicious circle of sticky mucus and further infections results.

Dornase alfa (rhDNase I) hydrolyses extra-cellular DNA from the neutrophils in the bronchial mucus, which increase it`s liquidity drastically. It is related to the natural enzyme doexyribonuclease I (DNase I) which is normally produced by the pancreas and salivary glands.

 

• Briefly explain what neonatal respiratory distress syndrome is, what the general treatment strategies involve and how cortisone and exogenous surfactants solve the problem.

Neonatal respiratory distress syndrome is also known as hyaline membrane disease.  The surface-active material which covers the respiratory unit of the airways is formed only in the last weeks of pregnancy.  When babies are born prematurely, this surface-active material has not yet formed, resulting in disrupted gas exchange and also the possibility that the lungs may collapse.  Treatment must follow rapidly in order to save the life of the premature baby.

General treatment strategies include oxygen to ensure oxygenation, ventilation used for positive pressure and drugs: exogenous sufactants (beractant and poractant alfa).

Cortisone: Boosts endogenous surfactant production and can be administered prophylactically.

Exogenous surfactants: Increases the lung surfactant.

 

• What is the role of oxygen therapy in neonatal respiratory distress syndrome?  What do the dangers of oxygen toxicity involve?

Oxygen (mixed with air at room temperature) is administered in order to ensure oxygenation.

A continuous positive pressure (as obtained with a ventilator) improves respiration and keeps the alveoli open to prevent collapse.  It is critically important that the arterial partial oxygen pressure is continuously monitored.

Sufficient oxygen is a basic requirement for normal respiration.  Therapeutically it is administered generally to prevent or reverse hypoxia (of various causes).  When oxygen is inhaled in excessive quantities and/or over too long a period of time, it has toxic effects.  Paradoxically, oxygen toxicity causes, inter alia, reduced gas exchange, hypoxia and, in extreme cases, death.  In neonates, it can cause retinal damage and blindness.

 

• Briefly explain what neonatal apnoea is and how the methylxanthines solve the problem.  Which methylxanthine is used?

Neonatal apnoea occurs when the respiratory centre in the medulla of the premature baby has not yet developed sufficiently to stimulate continuous breathing.  The breathing centre is, therefore, still insensitive to the stimulating effect of carbon dioxide.  Apnoea has a duration, typically, of longer than 15 seconds and is accompanied by bradycardia. Repeated episodes of apnoea with hypoxia can eventually lead to neural damage.

Methylxanthines, especially caffeine and theophylline, stimulate the central nervous system and intravenous administrations of these drugs usually help to solve the problem.  Therapy is however, usually discontinued as soon as possible – usually after a few weeks in intensive care.  The neonate then also receives oxygen therapy and the oxygen levels in the blood are continuously monitored.