Question

A 9-year-old female with cystic fibrosis presented to the pulmonary clinic with persistent exertional dyspnea and cough with scant sputum production. Physical assessment revealed normal vital signs, but she had an oxygen saturation of 91% while breathing room air. Her weight had fallen from 68.2 kg to 65.5 kg over the last 3 months. Cardiovascular assessment was completely normal. Lungs demonstrated coarse breath sounds bilaterally and were moderately decreased. The abdomen was normal, extremities demonstrated mild clubbing, and there was no peripheral edema. FEV1 had decreased from 70% to 50%. The chest radiograph resembled baseline findings with no obvious infil- trate or pneumothorax. Her standard inhaled treatment regimen was albuterol, 7% hypertonic saline, dornase alfa, and Flovent followed by vest therapy twice daily. She was prescribed a month-long course of azithromycin, aztreonam, and inhaled tobramycin for suspected pulmonary exacerbation with an acute superinfection. One month later she returned to the clinic for a follow-up visit. Physical assessment revealed moderate improvement in dyspnea as well as her FEV1, which now was back to baseline, and her oxygen saturation improved to 95% on room air.

1. What is the mechanism of action of dornase alfa?

Answer 1

Dornase alpha is an inhaled drug for treating cystic fibrosis, a lung disease which is the most common fatal genetic disease in developed countries. The lungs continually secrete fluid into the airways to keep them moist. In cystic fibrosis, the fluid becomes thick because the amount of water it contains is reduced. The thickened fluid is difficult to cough up or spit out. It blocks the airways, making breathing difficult and promoting the growth of bacteria and infection. Infection destroys the tissues of the lungs, and it is the slowly progressive destruction of the lungs that is the major cause of disability and death in children with cystic fibrosis. The thick fluid contains high concentrations of deoxyribonucleic acid (DNA). Dornase alpha is a genetically engineered form of the human enzyme, deoxyribonuclease or DNAse. Dornase alpha breaks down the DNA and thereby reduces the thickness of the fluids. Dornase alpha was approved by the FDA in 1993.