**Effect of altered gravity environments on aerosol deposition in the
human lung**

Chantal Darquenne and G. Kim Prisk

Dept. of Medicine, University of California, San Diego, USA

The deposition of aerosols in the human lung is primarily due to the
mechanisms of inertial impaction, gravitational sedimentation and
Brownian diffusion. Inertial impaction causes most of the particles
larger than 5 μm to deposit in the upper airways. Brownian diffusion
affects smaller particles (\<1 μm), which deposit mainly in the alveolar
region. Sedimentation is the gravitational settling of particles and
mainly affects particles in the size range 1 to 8 μm. Of these three
mechanisms, sedimentation is the only gravity-dependent process and is
changed in altered gravity environments.

We have undertaken an extensive experimental research program on the
effect of gravity on aerosol transport in the human lung. 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^1^. 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. However, in µG, deposition of the small
particles 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 unaccounted 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.

We then undertook a series of bolus deposition (DE) and dispersion (H)
studies in altered G levels^2,3^. A bolus containing 0.5, 1.0 or 2.0 μm
aerosol particles was introduced at predetermined points in an
inspiration from residual volume (RV) to 1 liter above functional
residual capacity. The inspiration was immediately followed by an
expiration to RV. Penetration volumes (V~p~) of the bolus ranged from
150 to 1500 ml. For each particle size (d~p~), the data showed that, at
shallow V~p~, DE and H were not different between gravity levels. In
contrast, at larger V~p~, 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 H with increasing V~p~ 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.

Recently, we performed a new series of bolus studies with a protocol
designed to induce complex folding patterns within the lung^4^. 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^5,6^. 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.^6^ in rat lungs after only one breathing cycle. Such a conclusion is
also important in the context of our total deposition studies^1^ as it
provides a mechanistic basis to explain what we previously described as
"enhanced diffusion resulting from unaccounted mixing effects".

[References]{.underline}

1\. Darquenne,C., M.Paiva, J.B.West, and G.K.Prisk. 1997. Effect of
microgravity and hypergravity on deposition of 0.5- to 3-µm-diameter
aerosol in the human lung. J. Appl. Physiol. 83:2029-2036.

2\. Darquenne,C., J.B.West, and G.K.Prisk. 1998. Deposition and
dispersion of 1 µm aerosol boluses in the human lung: Effect of micro-
and hypergravity. J. Appl. Physiol. 85:1252-1259.

3\. Darquenne,C., J.B.West, and G.K.Prisk. 1999. Dispersion of 0.5-2 mm
aerosol in micro- and hypergravity as a probe of convective
inhomogeneity in the human lung. J. Appl. Physiol. 86:1402-1409.

4\. Darquenne,C., and G.K.Prisk. 2004. Effect of small flow reversals on
aerosol mixing in the alveolar region of the huma lung. J. Appl.
Physiol. 97:2083-2089.

5\. Butler,J.P., and A.Tsuda. 1998. Effect of convective stretching and
folding on aerosol mixing deep in the lung, assessed by approximate
entropy. J. Appl. Physiol. 83:800-809.

6\. Tsuda,A., R.A.Rogers, P.E.Hydon, and J.P.Butler. 2002. Chaotic
mixing deep in the lung. Proc. Nat. Acad. Sci. USA 99:10173-10178.

This work was funded by NASA grant NAGW4372 and by NIH grant 1 RO1
ES11184