Inhalation therapy with recombinant human deoxyribonuclease I

Infections of the respiratory tract are often associated with production of purulent sputum. One of the most important components contributing to the abnormal rheological properties of this sputum is neutrophil-derived extracellular DNA. Recombinant human deoxyribonuclease I (rhDNase, dornase alfa) was developed as a therapeutic protein that is administered by inhalation of a nebulized aqueous solution to break up this DNA into small fragments, and thus to correct the viscoelastic properties of the sputum. The stability of rhDNase during storage and aerosol generation was investigated. The methodology used in these studies and in the quantitation of the therapeutic aerosol available to the patient is reviewed. The results of the key findings in the clinical trials in cystic fibrosis and other chronic obstructive pulmonary diseases are presented.