Physical properties, lung deposition modeling, and bioactivity of recombinant GM-CSF aerosolised with a highly efficient nebulizer.

Pulmonary alveolar proteinosis (PAP) is a rare condition characterized by the accumulation of lipoproteinaceous material within air spaces. Although whole lung lavage is the current standard of care, recent advances in our understanding of PAP pathophysiology suggest that the disorder may benefit from inhalation of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). The aim of this study was to determine the physical properties and bioactivity of rGM-CSF aerosolised by the highly efficient AKITA² APIXNEB® nebulizer system. The physical properties of aerosolised rGM-CSF were investigated in terms of droplet size, output and output rate by laser diffraction and gravimetrical analysis. Lung deposition was assessed using deposition modeling (ICRP). Molecular mass before and after aerosolisation was determined by SDS-PAGE, while the bioactivity of rGM-CSF was evaluated by measuring the GM-CSF-stimulated increase in pSTAT5 using mAM-hGM-R cells. Ninety-six % of the rGM-CSF filling dose was aerosolised with the Akita² Apixneb® nebulizer system. Particle size was highly reproducible, and the amount deposited within the lung was 80.35% of the delivered dose. The aerosolisation did not alter the molecular structure of rGM-CSF, nor its ability to stimulate the pSTAT5, which increased by 99.5%, similar to values for rGM-CSF prior to aerosolisation. We conclude that the highly efficient AKITA² APIXNEB® nebulizer system is likely to efficaciously deliver rGM-CSF to the airways of patients with autoimmune PAP.

Tooth extractions in patients under antiresorptive therapy for osteoporosis: Primary closure of the extraction socket with a mucoperiosteal flap versus application of platelet-rich fibrin for the prevention of antiresorptive agent-related osteonecrosis of the jaw.

PURPOSE: The aim of this study was to compare primary closure of the extraction socket to application of platelet-rich fibrin (PRF) without subsequent primary closure for the prevention of osteonecrosis of the jaw (ONJ) in patients administered antiresorptive therapy for osteoporosis. MATERIALS AND METHODS: Primary closure of the extraction socket was performed with a mucoperiosteal flap and two-layer suturing or PRF was inserted into the extraction socket without subsequent primary closure. In all patients, intra- and postoperative complications as well as the overall treatment outcome were recorded. RESULTS: The patient sample consisted of 77 patients; primary closure with a mucoperiosteal flap was performed in 39 patients (group A), and application of PRF without subsequent primary closure was performed in 38 patients (group B). There were no statistically significant differences (p > 0.05) between the two groups in terms of age and gender, duration and type of antiresorptive therapy, teeth to be extracted (number, location and type) as well as comorbidities. No intraoperative complications occurred in either of the groups. Postoperative complications were found in 6 patients in group A and in one patient in group B. Analyzing risk factors for these complications, the highest OR (6.72 with p = 0.085 in univariate analysis; 12.81 with p = 0.052 in multivariate analysis) was found for the type of procedure (group A/group B). All patients had complete mucosal coverage without any signs of antiresorptive agent-related osteonecrosis of the jaw at the final control examination 90 days postoperatively. CONCLUSION: Based on the results of this study, the use of PRF can be recommended as a preventive measure in patients requiring tooth extractions while being under antiresorptive therapy for osteoporosis.

The use of combined single photon emission computed tomography and X-ray computed tomography to assess the fate of inhaled aerosol.

BACKGROUND: Gamma camera imaging is widely used to assess pulmonary aerosol deposition. Conventional planar imaging provides limited information on its regional distribution. In this study, single photon emission computed tomography (SPECT) was used to describe deposition in three dimensions (3D) and combined with X-ray computed tomography (CT) to relate this to lung anatomy. Its performance was compared to planar imaging. METHODS: Ten SPECT/CT studies were performed on five healthy subjects following carefully controlled inhalation of radioaerosol from a nebulizer, using a variety of inhalation regimes. The 3D spatial distribution was assessed using a central-to-peripheral ratio (C/P) normalized to lung volume and for the right lung was compared to planar C/P analysis. The deposition by airway generation was calculated for each lung and the conducting airways deposition fraction compared to 24-h clearance. RESULTS: The 3D normalized C/P ratio correlated more closely with 24-h clearance than the 2D ratio for the right lung [coefficient of variation (COV), 9% compared to 15% p < 0.05]. Analysis of regional distribution was possible for both lungs in 3D but not in 2D due to overlap of the stomach on the left lung. The mean conducting airways deposition fraction from SPECT for both lungs was not significantly different from 24-h clearance (COV 18%). Both spatial and generational measures of central deposition were significantly higher for the left than for the right lung. CONCLUSIONS: Combined SPECT/CT enabled improved analysis of aerosol deposition from gamma camera imaging compared to planar imaging. 3D radionuclide imaging combined with anatomical information from CT and computer analysis is a useful approach for applications requiring regional information on deposition.