Reduced Gravity and Aerosol Deposition in the Human Lung

provides an overview of those studies as a basis for the consideration of aerosol deposition in the reduced gravity of Mars. Overall deposition: We first performed total deposition studies of 0.5-3 μm-diameter particles in normal gravity (1G), microgravity (μG) and hypergravity (~1.6G) using the NASA Microgravity Research Aircraft [2]. Subjects continuously breathed aerosol from a reservoir at a constant flow rate (~0.45 l/s) and breathing frequency (~15 breaths/min). Data showed that deposition increased with increasing G level. However, in μG, deposition of the small particles (~1μm) was higher than predicted by the numerical models. As inertia is negligible for these small particles and sedimentation is absent in μG, the higher deposition was explained by a larger deposition by enhanced diffusion resulting from previously unaccounted for mixing effects. While the overall change in total deposition caused by this process in 1G might be small, the effect may be disproportionately large if deposition occurs in the sensitive alveolar region of the lung, a region where the subsequent clearance of deposited particles is significantly slower than in the central airways [13]. Regional deposition: In order to probe the details of aerosol deposition, we undertook a series of bolus deposition (DE) and dispersion (H) studies in altered G levels [3-5]. A small bolus containing 0.5, 1.0 or 2.0 μm aerosol particles was introduced at predetermined points in an inspiration from residual volume to 1 liter above functional residual capacity. Penetration volumes (Vp) of the bolus ranged from 150 to 1500 ml, and in doing so directly probed deposition in the central airways (Vp= 150 ml), moving towards the periphery as penetration volume was increased. For each particle size, the data showed that, at shallow Vp (<200ml), DE and H were not different between gravity levels. In contrast, at larger Vp, when the aerosol bolus reached the alveolar regions of the lung, DE and H were strongly dependent on the G level. The steady increase in dispersion with increasing Vp suggests a continued presence of mixing processes in the early generations of the acinar region. This mixing may facilitate particles entering the alveolar cavities and eventually depositing. Understanding “enhanced diffusion”: We performed a series of bolus studies with a protocol designed to induce complex folding patterns within the lung [7]. Small flow reversals were imposed during a 10-sec breath-hold that followed the inspiration of 0.5 and 1 μm aerosol bolus. This protocol was based on the suggestion that irreversibility of alveolar flow combined with a stretched and folded pattern of streamlines can lead to a sudden increase in mixing and therefore deposition in the lung [14, 15]. Contrary to our expectations, the data showed that increasing the number of flow reversals had almost no effect on aerosol dispersion and deposition. We concluded that the mechanism of stretch and fold likely occurred during the one breathing cycle included in the basic maneuver. This conclusion is consistent with the complex mixing patterns observed by Tsuda et al. [14] in rat lungs after only one breathing cycle. This conclusion is important as it provides a mechanistic basis to explain what we previously described as “enhanced diffusion resulting from unaccounted mixing effects” that was found in our total deposition studies [2]. Retention of deposited particles in reduced gravity: The other important aspect of understanding aerosol effects in the lung is the residence time of the particles following deposition. Depending upon the lung region where particle deposit (airways versus alveolar region), these residence times differ by several orders of magnitude. The spatial distribution of coarse particles (MMAD ≈ 5 μm) deposited in the human lung was assessed using planar gamma scintigraphy [9]. Radiolabeled particles (Tc) were inhaled in a controlled fashion (0.5 l/s, 15 breaths/min) during multiple periods of μG aboard the NASA Microgravity Research Aircraft and in 1G. In both cases, deposition scans were obtained immediately post inhalation and at 1h30 min, 4h, and 22h post inhalation. Relative distribution of deposition between the airways and the 6008.pdf Dust in the Atmosphere of Mars 2017 (LPI Contrib. No. 1966)