RHDNASE-I AEROSOL DEPOSITION AND RELATED FACTORS IN CYSTIC-FIBROSIS

To identify factors influencing lung dose of aerosolized recombinant h uman deoxyribonuclease (rhDNase I), we used gamma camera and filter te chniques to measure deposition in 15 clinically stable patients with c ystic fibrosis (CF) (five males and 10 females, age 6-31 yr, mean 16.9 ) who were on chronic daily therapy. Total and regional deposition wer e correlated with breathing pattern, pulmonary function, demographic f actors, and disease severity. In addition, the effects of each patient 's measured lung dose on pulmonary function was estimated by stopping the drug and observing changes in spirometry over a 2-wk follow-up per iod. After discontinuance of the drug, all patients reported worsening of dyspnea and difficulty producing sputum. There was a significant d ecrease in FEV1 (% predicted, mean +/- SE, 86.9% +/- 5.57 to 77.8% +/- 5.73, p < 0.005), but all patients completed the study. In some patie nts, as much as 48% of the deposited aerosol was found in the pharynx (range 0.0 to 0.30 mg, mean 0.089 mg +/- 0.029), and pharyngeal deposi tion correlated negatively with tidal volume (r = -0.696, p < 0.006) a nd age (r = -0.743, p < 0.005). For the lungs, deposition ranged betwe en 0.16 mg and 0.78 mg of the 2.5 mg nebulizer dose (mean 0.47 +/- 0.0 4 mg) and correlated negatively with FEV1 (% predicted, r = -0.611, p = 0.0152). However, the spirometric decrements following cessation of therapy did not correlate with the lung dose of the drug. Analysis of regional deposition within the lungs indicated a wide range of distrib ution between central and peripheral zones. In conclusion, the deposit ion pattern of rhDNase I aerosols in patients with CF is largely influ enced by respiratory physiology, which itself depends upon age and sev erity of lung disease. As the patients grow there is a decrease in upp er airway deposition and more particles are presented to the lungs whe re those patients with more airways disease have enhanced pulmonary de position. Upper airway deposition of rhDNase I is significant, especia lly in younger patients, and may be related to laryngeal side effects.