RhDNase I aerosol deposition and related factors in cystic fibrosis

• Published in: American journal of respiratory and critical care medicine Vol. 156; no. 5; pp. 1662 - 1668
• Main Authors: DIOT, P, PALMER, L. B, SMALDONE, A, DECELIE-GERMANA, J, GRIMSON, R, SMALDONE, G. C
• Format: Journal Article
• Language: English
• Published: New York, NY American Lung Association 01.11.1997
• Subjects: Adolescent; Adult; Aerosols; Biological and medical sciences; Child; Cystic Fibrosis - diagnostic imaging; Cystic Fibrosis - drug therapy; Cystic Fibrosis - physiopathology; Deoxyribonuclease I - administration & dosage; Deoxyribonuclease I - pharmacokinetics; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Gamma Cameras; Humans; Lung - diagnostic imaging; Lung - metabolism; Male; Medical sciences; Pharmacology. Drug treatments; Radionuclide Imaging; Recombinant Proteins - administration & dosage; Respiratory system; Spirometry; Tidal Volume; Human; Chemotherapy; Treatment; Dornase alfa; Respiratory disease; Digestive diseases; Metabolic diseases; Aerosol deposition; Cystic fibrosis; Genetic disease; Pancreatic disease; Dose activity relation
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/ajrccm.156.5.9604093

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.