INHALATION-THERAPY WITH RECOMBINANT HUMAN DEOXYRIBONUCLEASE-I

Infections of the respiratory tract are often associated with producti on of purulent sputum. One of the most important components contributi ng to the abnormal rheological properties of this sputum is neutrophil -derived extracellular DNA. Recombinant human deoxyribonuclease I (rhD Nase, dornase alfa) was developed as a therapeutic protein that is adm inistered by inhalation of a nebulized aqueous solution to break up th is DNA into small fragments, and thus to correct the viscoelastic prop erties of the sputum. The stability of rhDNase during storage and aero sol generation was investigated. The methodology used in these studies and in the quantitation of the therapeutic aerosol available to the p atient is reviewed. The results of the key findings in the clinical tr ials in cystic fibrosis and other chronic obstructive pulmonary diseas es are presented.