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2611367 
Journal Article 
Abstract 
Aerosol characterization of nebulized GM-CSF 
Zimlich, WC; Mariani, F; Muellinger, B; Kadija, Z; Gleske, J; Kroneberg, P; Frey, M; Campo, I; Pozzi, E; Luisetti, M 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A5987 
English 
WOS:000208771004346 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Current pathophysiology concepts of autoimmune pulmonary alveolar proteinosis (PAP) suggest that lung infiltrates may benefit from supplementation of GM-CSF. Preliminary data showed that the inhalation route would be more effective than the s.c.one, with higher rate of responders. A clinical trial of inhaled GM-CSF in PAP patients has been designed and as a preliminary step, the particle size distribution and output measurements have been completed using the AKITA^2 APIXNEB inhalation system. The device has a highly efficient, breath actuated vibrating mesh nebulizer plus the system guides the patient through the inhalation process using controlled flow rate and inhalation volume to maximize drug deposition. The aim of this aerosol characterization is to demonstrate that the test formulation can be effectively delivered to the human lungs. Particle Size (PS) of the nebulized GM-CSF (Leukine, Bayer HC, USA) was determined by laser diffraction. Gravimetrical analysis indicated the Delivered Dose (DD, dose available for inspiration) and the Output Rate (nebulized amount/time). Lung dose was assessed using deposition modelling (ICRP). The results of PS showed a mean volume median diameter (VMD) of 4.31 ± 0.11 μm. DD was measured at 95.71 ± 0.073 % of 1ml filling dose. The mean continuous Output Rate was 1.043 ± 0.008 mL/min. The lung deposition modelling predicted that 80.35% of DD will deposit in the lungs using the controlled breathing pattern. The lung deposition of GM-CSF was calculated as 192.3 μg, from an initial loading dose of 250 μg. We conclude that the AKITA APIXNEB 2 nebulizer with a filling volume of 1 ml GM-CSF should lead to high lung deposition dose in patient volunteers. Thus we are hopeful that the highly effective in vitro performance of the AKITA^2 APIXNEB nebulizer system with GM-CSF formulation will lead to a positive in vivo result in patients affected by autoimmune PAP. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010