To identify factors influencing lung dose of aerosolized recombinant human
deoxyribonuclease (
rhDNase I), we used
gamma camera and filter techniques to measure deposition in 15 clinically stable patients with
cystic fibrosis (CF) (five males and 10 females, age 6-31 yr, mean 16.9) who were on chronic daily
therapy. Total and regional deposition were correlated with breathing pattern, pulmonary function, demographic factors, 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 period. After discontinuance of the
drug, all patients reported worsening of
dyspnea and difficulty producing sputum. There was a significant decrease 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 patients, 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 deposition correlated negatively with tidal volume (r = -0.696, p < 0.006) and age (r = -0.743, p < 0.005). For the lungs, deposition ranged between 0.16 mg and 0.78 mg of the 2.5 mg
nebulizer dose (mean 0.47 +/- 0.04 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 distribution between central and peripheral zones. In conclusion, the deposition pattern of
rhDNase I
aerosols in patients with CF is largely influenced by respiratory physiology, which itself depends upon age and severity of
lung disease. As the patients grow there is a decrease in upper airway deposition and more particles are presented to the lungs where those patients with more airways disease have enhanced pulmonary deposition. Upper airway deposition of
rhDNase I is significant, especially in younger patients, and may be related to laryngeal side effects.