Removal of sedimentation decreases relative deposition of coarse particles in the lung periphery

Abstract

Lung deposition of >0.5-μm particles is strongly influenced by gravitational sedimentation, with deposition being reduced in microgravity (μG) compared with normal gravity (1G). Gravity not only affects total deposition, but may also alter regional deposition. Using gamma scintigraphy, we measured the distribution of regional deposition and retention of radiolabeled particles ((99m)Tc-labeled sulfur colloid, 5-μm diameter) in five healthy volunteers. Particles were inhaled in a controlled fashion (0.5 l/s, 15 breaths/min) during multiple periods of μG aboard the National Aeronautics and Space Administration Microgravity Research Aircraft and in 1G. In both cases, deposition scans were obtained immediately postinhalation and at 1 h 30 min, 4 h, and 22 h postinhalation. Regional deposition was characterized by the central-to-peripheral ratio and by the skew of the distribution of deposited particles on scans acquired directly postinhalation. Relative distribution of deposition between the airways and the alveolar region was derived from data acquired at the various time points. Compared with inhalation in 1G, subjects show an increase in central-to-peripheral ratio (P = 0.043), skew (P = 0.043), and tracheobronchial deposition (P < 0.001) when particles were inhaled in μG. The absence of gravity caused fewer particles to deposit in the lung periphery than in the central region where deposition occurred mainly in the airways in μG. Furthermore, the increased skew observed in μG likely illustrates the presence of localized areas of deposition, i.e., "hot spots", resulting from inertial impaction. In conclusion, gravity has a significant effect on deposition patterns of coarse particles, with most of deposition occurring in the alveolar region in 1G but in the large airways in μG.

Microgravity and the respiratory system

“…For large particles (,5 mm), impaction results in increased relative deposition in the central airways, where clearance mechanisms are effective [80], but for smaller particles (,1 mm), the suggestion is that alveolar deposition will be increased [81], raising the possibility that these particles will be retained in the lung for a longer period of time, enhancing their toxic potential.…”

Effect of Posture on Regional Deposition of Coarse Particles in the Healthy Human Lung

“…(6) Second, posture may be important for targeted inhaled drug delivery: (7) if posture does influence the spatial distribution of deposition, different postures can potentially be used to optimize targeting of inhaled drugs, not only in respiratory diseases, (8,9) but also targeted delivery to the systemic circulation. (10) Previous work from our group highlighted the role of sedimentation in the redistribution of deposited coarse particles (11) by delivering aerosol particles during short periods of microgravity. Removal of gravitational sedimentation during the delivery of coarse particles increased the relative number of particles deposited in the large airways and decreased the relative portion of particles that deposited in the lung periphery.…”

Aerosol Deposition in the Human Lung in Reduced Gravity

“…Darquenne and colleagues (43) delivered aerosolized 0.9-lm-diameter particles to spontaneously breathing rats in both lG and 1G and measured aerosol deposition in these animals using postmortem magnetic resonance imaging techniques. (12) Comparing deposition in the central (C) region of the lung to that in the peripheral (P) region through the C/P ratio, they showed a reduced C/P ratio in lG compatible with an increase in the relative contribution of peripheral deposition to overall deposition. Even though there are major differences between rats and humans in terms of both airway tree structure (45,46) and ventilation distribution between dependent and nondependent regions of the lungs, (47,48) these animal data support the concept of an increased relative deposition of fine particles (i.e., 0.9 lm) in the lung periphery in the absence of gravity, in agreement with the indirect assessment from aerosol bolus tests described above (Fig.…”

“…(12) Particles were inhaled over multiple periods of lG during parabolic flights and in 1G. By collecting data immediately post inhalation and up to 22 hr post deposition, they determined the retention and distribution of deposited particles in the large, intermediate, and small airways as well as in the alveolar region (Fig.…”

“…It was not until the mid-1990s that more extensive measurements of aerosol deposition in reduced gravity were made. (5)(6)(7)(8)(9)(10)(11)(12)(13)(14) To date, all experimental studies on aerosol inhalation in reduced gravity have been performed during short periods of reduced gravity achieved during parabolic flights. The aim of this article is to review these experimental studies and highlight the role of gravity in the transport and deposition of inhaled particles in the human lung.…”