10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
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Regional Lung Deposition of Nebulized Hypertonic Saline for Trans-Nasal vs. Oral Inhalation in Healthy, Non-Smoking Adults
WILLIAM BENNETT, Kirby Zeman, Landon Holbrook, Katie Howe, Jihong Wu, David Busick, Richard Boucher, Scott Donaldson, University of North Carolina at Chapel Hill
Abstract Number: 1066 Working Group: Aerosols in Medicine
Abstract Background: Nebulized, hypertonic saline (7%) (HS) has been shown to improve hydration of cystic fibrosis (CF) airway surfaces, improving both mucociliary clearance and lung function in these patients. We previously demonstrated by gamma scintigraphy that a transnasal Pulmonary Aerosol Delivery device (tPAD; Parion Sciences, Inc., Durham, NC) is able to deliver a HS aerosol to the lungs as efficiently as a standard oral nebulizer (Pari LC Star) but with slightly more peripheral airway deposition as determined by the central/peripheral (C/P) ratio of deposited activity (Zeman et al, J Aerosol Med Pulm Drug Deliv. 30:223, 2017). Because there is uncertainty in the ability for C/P to accurately characterize airway vs. alveolar deposition we speculated that adding insoluble, particle clearance measures post-initial deposition would improve the resolution of aerosol deposition in the various airway generations of the lung.
Methods: Regional deposition for both devices was characterized by measuring the % clearance of inhaled radiolabelled (Tc99m) sulfur colloid particles (in 7% HS) using gamma scintigraphy over 24 h in healthy volunteers (n=5). The traditional C/P ratio was also calculated from the initial deposition image (normalized to a Cobalt57 transmission image for each subject). Airway deposition within bronchial airways (large, intermediate, and small) was estimated as % clearance of the insoluble labeled particles through 24 hours post deposition (Aw). Within the bronchial airways we estimated regional deposition in large airways as % clearance through 3-hour post deposition (LargeAw); large and intermediate airway as % clearance through 6 hours (Large/InterAw); and small airways as the % clearance between 6 and 24 hours (SmallAw). For both inhalation modalities, spontaneous flows/volumes were measured by a pneumotachograph during exhalation. Particle size for the tPAD was designed to be sufficiently small to minimize nasal deposition [volume median diameter (VMD)=1.3 um], and was 3.1 um for the LC Star.
Results: Mean tidal flows and volumes were similar for breathing on the tPAD vs. LC Star, 0.32 vs. 0.24 L/sec and 0.93 vs. 0.80 L. Both devices achieved similar % lung deposition relative to delivered dose, % lung = 30.7 vs. 35.4 for the tPAD vs. LC Star. Percent (%) extrathoracic deposition was also similar = 8.1 (tPAD) vs. 5.7 (LC Star). While the C/P ratios for the initial deposition were not different, 1.16 (tPAD) vs. 1.14 (LC Star), the Aw distribution tended to be less for the tPAD vs. LC Star, 9.7 vs. 21.9% respectively (p = 0.22). LargeAw distribution was significantly less for the tPAD vs. LC Star, 2.4 vs. 12.5%, as was Large/InterAw, 2.6 vs. 13.3% respectively (p < 0.05 by Wilcoxon signed-rank test). SmallAw distribution was similar between the two devices, 7 (tPAD) and 8.5 (LC Star) %.
Conclusions: The distribution of inhaled aerosol deposition via the tPAD and LC Star appeared to be equivalent using standard deposition measures, e.g., % lung deposition and C/P ratio. However, using measurements of clearance for the deposited insoluble, radiolabeled particles we were able to discern clear differences in regional deposition within large and intermediate airways between the two devices. Such clearance measurements should be considered to provide better resolution for regional deposition of nebulized, aerosolized drug delivery. Supported by NIH P01 HL108808 and Parion Sciences, Inc.