EFFECT OF SMALLER DROPLET SIZE OF DORNASE-ALPHA ON LUNG-FUNCTION IN MILD CYSTIC-FIBROSIS

Aerosolized recombinant human DNase (dornase alfa) reduces mucus visco elasticity in vitro and improves pulmonary function in patients with c ystic fibrosis (CF). We postulated that if dornase alfa could be deliv ered more peripherally to small airways in the lung in the form of sma ller aerosol droplets in patients with early airway obstruction, the i ncrease in pulmonary function from baseline might be improved. CF pati ents (n = 749) with mild lung disease (baseline forced vital capacity greater than or equal to 70% predicted) were randomly assigned to rece ive dornase alfa 2.5 mg daily for 2 weeks by one of two nebulizer syst ems: 1) the Medic-Aid Durable SideStream nebulizer powered by the Mobi lAire Compressor (SS/MA) producing a droplet size with a mass median a erodynamic diameter (MMAD) of 2.1 mu m; or 2) the Hudson T Up-draft ne bulizer with a DeVilbiss Pulmo-Aide compressor (HT/PA) with an MMAD of 4.9 mu m. Spirometry was performed at baseline and following 14 days of treatment. Dornase alfa delivered by both nebulizer systems produce d small but statistically significant improvements in pulmonary functi on compared with baseline. There was a trend (P = 0.06) toward greater improvement in forced expiratory flow in 1 s in the SS/MA group (4.3% ) compared with the HT/PA group (2.5%). These results indicate that th e short-term spirometric response to dornase alfa is influenced in par t by the physical characteristics of the aerosol in patients with mild lung disease. We speculate that this may be true for other therapeuti c aerosols, and it appears that localization of disease in the lung pl ays a role in the response to inhaled agents. (C) 1998 Wiley-Liss, Inc .