INTRODUCTION

Top Abstract Introduction Methods Results Discussion References

THERE IS A NEED TO BETTER UNDERSTAND the penetration and dispersion of aerosols in the lung as well as their ultimate deposition, whether the exposure occurs because of atmospheric pollution, occupational factors, or respiratory therapy. Aerosol dispersion results from mixing in the lung, and its measurement is a means of studying this process. Indeed, aerosols may be considered as a "nondiffusing gas" and may, therefore, be used to study the convective mixing occurring in the distal airways of the lungs without the confounding effect of diffusion always present in gas studies. The technique of aerosol bolus inhalation has been widely used to estimate aerosol dispersion in the respiratory tract (1, 4, 5, 11, 20). Particles deviate from the flow of the carrier gas by three mechanisms: diffusion, sedimentation, and inertia. Of these mechanisms, only sedimentation is a gravity (G)-dependent process. Because the lung distorts under its own weight, G force is also responsible for differences in regional ventilation (10, 14). Changes in the G level are, therefore, expected to affect the distribution of ventilation and the dispersion and deposition of aerosols, both because of changes in sedimentation and because of changes in regional ventilation.

To date, only two experimental studies have been reported on the effects of G on aerosol deposition. Hoffman and Billingham (12) collected deposition data with 2-µm-diameter particles in three subjects aboard a National Aeronautics and Space Administration (NASA) research aircraft. They found an almost linear increase in deposition with increasing G in the range of 0-2 G. More recently, Darquenne et al. (8) measured deposition of 0.5-, 1-, 2-, and 3-µm-diameter particles in four subjects on the ground and aboard the NASA research aircraft both in microgravity (µG) and at ~1.6 G. For 2- and 3-µm particles, their results were similar to those of Hoffman and Billingham (12) in that they found a nearly linear increase in deposition as a function of the G level. However, for 0.5- and 1-µm particles, deposition increased less between µG and 1 G than between 1 G and ~1.6 G. Thus deposition of the small particles in µG was higher than that predicted based on the hypergravity results and also based on existing models of aerosol deposition in the human lung. These results might be explained by two factors: first, a larger deposition by diffusion because of a higher alveolar concentration of aerosol in µG, since sedimentation is absent, and, second, the nonreversibility of the flow in the small airways, causing additional mixing of the aerosols.

In the present study, we performed aerosol bolus inhalations in normal subjects using 1-µm-diameter particles. We chose 1-µm-diameter particles because this was the size that showed the greatest discrepancy between predicted and actual deposition in µG in our previous study (8). Data were collected on the ground (in 1 G) and aboard the NASA Microgravity Research Aircraft in the weightless phase (µG) and in the ~1.6-G pullout phase. This paper reports the first results of bolus tests performed at different G levels in the human lung. The 1-G data were compared with previous studies (4, 7). The comparison of data obtained in µG and ~1.6 G with data obtained in 1 G helps to elucidate the effect of G on deposition and dispersion processes.

	METHODS

Top Abstract Introduction Methods Results Discussion References

Equipment. Aerosol bolus data were collected by using the equipment shown in Fig. 1. One position of the sliding valve SV1 allowed the subject to breathe air from the room through a two-way non-rebreathing valve equipped with filters. In the other position of the valve, the subject inspired the aerosol bolus located between the sliding valves SV2 and SV3, providing a bolus volume of ~70 ml. The measurement of the aerosol concentration and the flow rate were provided by a photometer (model 993000, PARI) (24) and a Validyne differential pressure transducer M-45 connected via short tubes to the two ports of a pneumotachograph (Fleisch no. 1, OEM Medical), respectively. The photometer, the pneumotachograph, and the valves were heated to body temperature to prevent water condensation. A diffusion dryer (dead space = 11 ml) was located between the photometer and the mouthpiece. It removed the water vapor from the exhaled air to avoid condensation on the lenses of the photometer. No significant differences were found in the analysis of the data obtained from bolus inhalations performed with and without the diffusion dryer positioned between the photometer and the mouthpiece. We included the diffusion dryer to minimize the effects of water vapor during the long series of measurements mandated by the NASA Microgravity Research Aircraft flight profile.

View larger version (25K): [in this window] [in a new window]   Fig. 1.   Schematic representation of experimental setup. One configuration of sliding valve (SV) SV1 allowed the subject to breathe air from the room through a 2-way non-rebreathing valve (NRV) equipped with filters. In the other configuration of valve, subject inspired aerosol bolus located between SV2 and SV3. Measurements of aerosol concentration and flow rate are provided by a photometer and a pneumotachograph (Fleisch no. 1), respectively. A diffusion dryer is located between the photometer and the mouthpiece to remove water vapors from exhaled air.

Aerosol generation. The bolus tube was filled with aerosol-containing monodisperse polystyrene latex particles (Duke Scientific). The particles were supplied in suspension (water), and the concentrate was diluted and dispensed via two Acorn II nebulizers (Marquest Medical Products). Before entering the bolus tube, the aerosol flows through a heated hose and a diffusion dryer to remove water droplets. The size of the spherical particles as specified by the manufacturer was 1.07 ± 0.014 (SD) µm. The aerosol concentration in the bolus tube was ~10⁴ particles/ml air.

The aerosol generated by the nebulizers was checked with a particle sizer (PCS-2000 Special, PALAS). The size analysis confirmed the size of the particles given by the manufacturer and shows that the amount of doublets in the aerosol was <5%. Tests using conductive tubing showed no significant effect from possible electrostatic charges on the particles.

Data recording and analysis. A personal computer (IBM ThinkPad 360 CSE) equipped with a 12-bit analog-to-digital card (National Instrument, DAQ700) was used for data acquisition. Signals from the photometer, a G sensor, a barometric pressure transducer, and the pneumotachograph were sampled at 100 Hz. Custom software was developed for the data acquisition using National Instruments Lab Windows CVI.

Data were collected on the ground and aboard the NASA Microgravity Research Aircraft. A typical flight consisted of a climb to an altitude of ~10,000 m, with the cabin pressurized to ~600 Torr. A "roller coaster" flight profile was then performed. The aircraft was pitched up at ~1.6 head-to-foot acceleration to a 45° nose-high attitude. Then the nose was lowered to abolish wing lift, and thrust was reduced to balance drag (thus maintaining µG). A ballistic flight profile resulted and was maintained until the aircraft nose was 45° below the horizon. In this manner, µG was maintained for ~27 s. A pullout averaging ~1.6 head-to-foot acceleration was maintained for ~40 s, causing the nose to pitch up to a 45° nose-high attitude, and allowed the cycle to be repeated. For convenience, the ~1.6-G hypergravity phase will be referred to as 1.6 G in the text.

Subjects and protocol. Four healthy subjects participated in the study. These were the same four subjects that participated in the previous study (8), and we retained their subject number for comparison purposes. Their relevant anthropometric data are listed in Table 1. After a few normal breaths, the subject exhaled to residual volume (RV) to ensure a known lung volume starting point. As functional residual capacity (FRC) varies significantly with G level (9, 17), we chose to use the more stable RV as the starting point for the test breath. Although there is some small change in RV in µG (9), the effect on our measurements is small. The test breath consisted of an inspiration from RV to FRC +1 liter at a flow rate of ~0.45 l/s, immediately followed by an expiration to RV, also at a flow rate of ~0.45 l/s. A flowmeter provided visual feedback to the subject. FRC refers to the seated 1-G FRC of the subject, and it was fixed for all experiments on that subject. During the inspiration, an aerosol bolus of ~70 ml was introduced at different penetration volumes (V_p) ranging from 200 to 1,500 ml. The V_p was defined as the volume of air inhaled from the mode of the aerosol bolus to the end of the inhalation.

The protocol was repeated four times for each V_p, both in µG and in 1.6 G. Before the flight, a set of data was also collected on the ground (1 G) with the same protocol. The protocol was approved both by the Committee on Investigations Involving Human Subjects at the University of California, San Diego, and by the Institutional Review Board at the Johnson Space Center, Houston, TX.

Data analysis. For each bolus test, three different parameters were calculated. They were the aerosol deposition, the aerosol dispersion, and the mode shift (MS). Deposition (DE) was calculated by using the following equation

(1)

where N_in and N_ex are the number of particles in the inspired and expired bolus, respectively. N_in and N_ex were calculated from the integration of the aerosol concentration as a function of the respired air. The integration was only done when the concentration exceeded 5% of the maximal expired concentration to reduce error due to the noise of the signal. An original tracing is shown in Fig. 2 for a bolus inhaled at a V_p of 500 ml. The shaded areas represent the portion of the inhaled and exhaled tracing where the aerosol concentration C(V) 0.05 C_max,ex(V) [C_max,ex(V) refers to the maximum concentration of the expired bolus]. The definition of the shaded zone is better displayed on the exhaled bolus (Fig. 2B) where the aerosol axis has been magnified. The 5% cutoff was chosen based on the noise-to-signal ratio of the aerosol tracings obtained aboard the aircraft, which was higher than the noise-to-signal ratio of the 1-G tracings. In 1 G, differences between deposition computed with no cutoff of the signal and a 5% cutoff was <2% at all V_p values.

View larger version (23K): [in this window] [in a new window]   Fig. 2.   Original tracing of aerosol bolus for penetration volume (Vp) = 500 ml. Concentration (C) is normalized to the maximum concentration of inhaled bolus. Shaded zones represent portion of the curve where C 0.05 maximum concentration of exhaled bolus (Cmax,ex) and where integration of the signal was computed. A: Hin, half-width of inspired bolus; Clim, threshold concentration above which concentration values are considered. B: zoom of the tracing; Hex, half-width of expired bolus; Mex, mode of expired bolus.

On a graph of aerosol concentration as a function of the respired volume, the half-width is defined as the bolus width (in ml) between the two points of one-half the maximum concentration of the bolus (Fig. 2). The change in half-width (H) reflecting the aerosol dispersion was obtained by the following equation

(2)

where H_in and H_ex are the half-widths of the inspired and expired boluses, respectively. Only the volumes at one-half the maximum concentration of the bolus are required to compute H_in and H_ex. Therefore, their computation is not influenced by the 5% cutoff of the signal used in the deposition calculation.

The MS was defined as the difference between the position of the peak of the expired bolus (M_ex) and the volume penetration of the inspired bolus (Fig. 2)

(3)

A negative value of MS indicates that the position of the mode of the expired bolus has shifted to a smaller lung volume than the location of the inspired bolus, i.e., that the bolus has moved toward the mouth.

Statistical analysis was performed by using Systat V5.0 (Systat, Evanston, IL). Measurements performed for the same experimental conditions with the same subject were not averaged before the statistical analysis was performed. Data were grouped in different categorial variables such as G level (µG, 1 G, and 1.6 G), V_p (200, 400, 600, 800, 1,000, 1,200, and 1,500 ml), and subject number. A two-way analysis of variance was performed to test for differences between the chosen categorial variables. Post hoc testing using Bonferroni adjustment was performed for tests showing significant F-ratios. Significant differences were accepted at the P < 0.05 level.

	RESULTS

Top Abstract Introduction Methods Results Discussion References

Bolus inhalations were performed on four healthy subjects for all V_p values ranging from 200 to 1,500 ml. However, at 1.6 G, because of high deposition, the expired bolus tracings we recorded for V_p >800 ml had too high a noise-to-signal ratio and the data were discarded.

Deposition. The effect of G level on the deposition of the aerosol bolus is displayed in Fig. 3. Figure 3A shows the deposition averaged over the four subjects (means ± SD). The data were not significantly different from one G level to the other for V_p = 200 ml and were significantly different for V_p >200 ml (P < 0.05), with lower deposition being present at lower G levels. At V_p = 400 and 600 ml, significant differences were found between data in µG and 1.6 G and between data in 1 G and 1.6 G but not between data in µG and 1 G. At each G level, deposition increases with increasing V_p. In µG, deposition varies from 18% at V_p = 200 ml to 50% at V_p = 1,500 ml. In 1 G, it varies from 14% at V_p = 200 ml to 69% at V_p = 1,500 ml; and at 1.6 G, it varies from 14% at V_p = 200 ml to 57% at V_p = 800 ml. The slope of the regression lines of deposition as a function of V_p is displayed in Fig. 3B (means ± SD). They are 0.023, 0.046, and 0.075%/ml in µG, 1 G, and 1.6 G, respectively.

View larger version (20K): [in this window] [in a new window]   Fig. 3.   Deposition of aerosol bolus. A: data are means ± SD, averaged over the 4 subjects as a function of Vp. , Microgravity (µG); , 1 G; , 1.6 G. * Significantly different compared with 1-G data, P < 0.05. B: slope of the regression lines between deposition and Vp for different gravity levels.

Dispersion. Figure 4A shows the dispersion as a function of V_p for each G level. Data were averaged over the four subjects (means ± SD). For V_p 400 ml, dispersion was strongly G dependent, with the greatest dispersion occurring for the largest G level. For V_p = 200 ml, there was a significant difference in dispersion values between µG and 1.6 G but not between µG and 1 G and between 1 G and 1.6 G. For each G level, dispersion was an approximately linear function of V_p. The slope of the linear regressions between dispersion and V_p are displayed in Fig. 4B (means ± SD). They are 0.19, 0.53, and 0.65 ml/ml in µG, 1 G, and 1.6 G, respectively.

View larger version (20K): [in this window] [in a new window]   Fig. 4.   Aerosol bolus dispersion. A: data are means ± SD, averaged over the 4 subjects as a function of Vp. , µG; , 1 G; , 1.6 G. * Significantly different compared with 1-G data, P < 0.05. B: slope of regression lines between dispersion and Vp for different gravity levels.

MS. Figure 5 shows the effect of the G level on the MS. The MS is plotted on Fig. 5A as a function of V_p. At each G level, the MS becomes increasingly negative with increasing V_p. For a given V_p >800 ml, significant differences were found between G levels, with MS becoming more and more negative (the bolus moving mouthward) with increasing G level. For V_p <800 ml, there were no significant differences. At V_p = 800 ml, there was a significant difference only between µG and 1.6 G. Regression between MS and V_p at each G level was calculated. The slopes of these lines are displayed in Fig. 5B (means ± SD). Whereas the slope in µG was lower than in 1 G, no significant differences were found between the slope in 1 G and in 1.6 G. 

View larger version (21K): [in this window] [in a new window]   Fig. 5.   Mode shift of bolus. A: data are means ± SD, averaged over the 4 subjects as a function of Vp. , µG; , 1 G; , 1.6 G. * Significantly different compared with 1-G data, P < 0.05. B: slope of regression lines between mode shift and Vp for different gravity levels.

	DISCUSSION

Top Abstract Introduction Methods Results Discussion References

Deposition. This study reports the effect of G level on the deposition and dispersion of 1-µm aerosol boluses inhaled to various volumetric depths within the lung. Figure 3 illustrates the deposition of aerosol as a function of the V_p. Deposition increases with increasing V_p for each G level. Deposition is usually attributed to three main mechanisms: inertial impaction, gravitational sedimentation, and Brownian diffusion. For 1-µm-diameter particles, gravitational sedimentation is the mechanism that affects the most deposition in 1 G. The settling velocity of the spherical particles is ~33 µm/s in 1 G, whereas the Brownian displacement in 1 s is only ~13 µm (3). Inertial impaction is negligible for this particle size. In a previous study by our group (8), we computed the contribution of these three deposition mechanisms for a full inspiration of 1-µm-diameter particles with a one-dimensional model of the aerosol transport and deposition in the human lung. In 1 G, we found that deposition by impaction, sedimentation, and Brownian diffusion was 2.2, 78.6, and 19.2% of total deposition, respectively.

Gravitational sedimentation takes place primarily in the distal part of the lung where residence time in airways is high and airway dimensions are small. At each G level, deposition increases with V_p as the aerosol bolus probes more distal airways (Fig. 3A). This can be referred to as the "penetration effect." The increase in deposition may also be attributed to a "time effect." By increasing the V_p, the bolus enters the respiratory tract earlier in the inspiration and, therefore, more time is available to the particles to deposit. Both effects contribute to the deposition we measured in these experiments.

For a given V_p, deposition increases with G level. Of the three mechanisms of deposition, sedimentation is the only G-dependent process. Sedimentation is, therefore, the mechanism to account for the increased deposition in 1.6 G compared with 1 G. For V_p <400 ml, deposition was, however, not significantly different from one G level to the other, confirming that deposition by sedimentation is a process that takes place primarily in the periphery of the lung.

In µG, as inertia is negligible, deposition can only be attributed to diffusion. However, Brownian diffusion by itself does not explain the deposition values we measured in µG. Indeed, for V_p >400 ml where significant differences were found between G levels, deposition in µG is more than one-half the deposition in 1 G, which would imply that Brownian diffusion is the predominant mechanism of transfer of particles to the lung. This is in contradiction with the difference between the settling and diffusive velocity of these particles.

In a previous study (8), we observed a higher intrapulmonary deposition for small particles in µG than predicted by numerical models. The higher deposition was then explained by the nonreversibility of the flow and by a larger deposition by diffusion due to a higher alveolar concentration of aerosol in the absence of G. The nonreversibility of the flow was mainly explained by the asymmetry in the velocity profiles between inspiration and expiration. Very recently, Otani et al. (16) studied low-Reynolds-number cyclic flows in an alveolus model. They showed that these flows are irreversible, despite the low Reynolds number, causing substantial convective mixing in the periphery of the lung. The nonreversibility of the flow results in an additional mixing effect that moves the particles in the direction of the alveoli, increasing the apparent contribution of diffusional loss of particles in the lung. This increase in diffusional loss might explain the high deposition values we measured in µG in the present study.

Aerosol dispersion. Figure 4 illustrates the dispersion of aerosol as a function of the V_p. Dispersion is attributed to Brownian diffusion and convective mixing. As defined by Heyder et al. (11), convective mixing refers to all the mechanisms, except Brownian diffusion, which transport particles from tidal to residual gas. Convective mixing causes dispersion of aerosol boluses, depending on factors such as velocity patterns, airway and alveolar geometries, asymmetries between inspiratory and expiratory flows, inhomogeneous ventilation of the lung, and cardiogenic mixing.

Velocity profiles in the airways are not uniform and allow particles at different radial positions in the airways to travel at different speed (21). The branching structure of the bronchial tree also imparts a directional asymmetry to the flow field, manifested by a difference in the shape of the velocity profile during inspiration and expiration. During inspiration, airflow is most rapid at the center of the airways, so that the aerosol bolus entering the lung is surrounded by a sheath of residual gas that is largely particle-free. Thus particles in the center of the airways reach more distal generations of the respiratory tract than do particles located near the walls of the airways, where velocities are smaller. During expiration, the velocity profile is more blunted, and particles in the center of the airways travel at a slower rate than during inspiration, whereas particles near the walls travel faster, preventing the bolus from recovering its original shape.

Ventilation inhomogeneities may be described by two mechanisms: convection-dependent ventilatory inhomogeneities (15) and diffusive processes. Whereas diffusive processes are responsible for ~30% of inhomogeneities of gas concentrations in 1 G (6), this mechanism is negligible for particles of 1 µm in size, as their diffusion coefficient is more than an order of magnitude lower than that of gases. Prisk et al. (18) showed in a study on ventilatory inhomogeneities determined from multiple-breath washouts during sustained µG that there was a reduction in the contribution of convection-dependent ventilatory inhomogeneities to overall ventilatory inhomogeneity. They concluded, however, that a considerable proportion of the inhomogeneity of ventilation present in the upright lung at 1 G during tidal breathing is nongravitational in origin. These ventilatory inhomogeneities also increase dispersion.

Rosenthal (19) showed in a theoretical study that ventilatory inhomogeneities should increase dispersion. Indirect experimental evidence of this statement can be found in a study by Anderson et al. (2) in which bolus aerosol dispersion was measured in normal subjects and in patients with cystic fibrosis (CF). CF is an obstructive disease that is known to increase inhomogeneities of ventilation. According to this paper, studies of pulmonary mechanics in patients with CF have shown an increase in the inhomogeneities of ventilation distribution. Anderson et al. showed that patients with CF exhaled boluses that were broader than those exhaled by normal subjects at all V_p values they examined (V_p = 100-700 ml). These authors believed that the increased bolus spreading in patients with CF was partly due to the increased inhomogeneities in ventilation distribution, compared with normal subjects. In our study, we modified the level of ventilatory inhomogeneities in healthy subjects by performing the test in µG where ventilatory inhomogeneities are still present (18, 23) but reduced, compared with normal G. We obtained lower dispersion values in µG than in 1 G.

Particles sediment during their transport in the airways and, therefore, do not follow the air streamlines. This effect is negligible in the first generations of the lung where bulk velocity is an order of magnitude larger than the settling velocity of the 1-µm-diameter particles. In the distal part of the lung, the radial position of the particles may significantly change while flowing through airways. However, according to Schulz et al. (22), who studied the convective and diffusive gas transport in canine intrapulmonary airways, the sedimentation rate does not affect significantly aerosol dispersion. They performed aerosol bolus inhalations in 1 G with 0.86 and 2.38-µm-diameter particles (a 7.7 times difference in settling velocity) and yet found no systematic differences between the dispersion of the smaller and the larger particles.

The convective mixing occurring over a single breathing cycle is the phenomenon assessed by aerosol bolus dispersion. The data we collected in this study highlight the effect of G on this phenomenon. As shown in Fig. 4A, for each G level, dispersion increases continuously with increasing V_p, indicating that each subsequent airway generation of the lung contributes to convective mixing. In the studied range of V_p values, this increase is approximately linear and is shown in the slope of the regression lines of dispersion as a function of V_p (Fig. 4B). For a given V_p, dispersion increases with G level: likely factors include the uneven distribution of ventilation and the asynchrony in regional filling and emptying of the lung, both of which increase with G.

However, while dispersion is lower in µG than in 1 G, it still increased steadily with increasing V_p, showing that nongravitational ventilatory inhomogeneity is partly responsible for dispersion. Although total ventilation inhomogeneity is reduced in µG, G-independent ventilatory inhomogeneities are still present and contribute to aerosol dispersion, as do cardiogenic oscillations, differences in velocity patterns between inspiration and expiration, the effect of secondary flow mixing at bifurcations, and laryngeal jetting. Although all these mechanisms may contribute to aerosol dispersion, the continuing presence of ventilatory inhomogeneities in µG (18, 23) suggests that aerosol dispersion in µG is largely due to nongravitational ventilatory inhomogeneities.

The relative contribution of G to dispersion also increases with V_p (Fig. 4). At V_p = 200 ml, no significant differences were found between dispersion at different G levels, whereas at V_p = 1,500 ml, dispersion in µG is only 51% of dispersion in 1 G. Based on the slope of the regression lines (Fig. 4B), dispersion due to G-independent factors is 36% of overall dispersion in 1 G and 30% of overall dispersion in 1.6 G. According to Verbanck et al. (23), the G-independent ventilatory inhomogeneities are at least as large as the G-dependent ventilatory inhomogeneities for gases. Our data show a lower contribution of the G-independent inhomogeneities to the overall dispersion than would be expected from the study by Verbanck et al. This might be explained by the absence of diffusion inhomogeneities in the aerosol experiments, which reduces the G-independent ventilation inhomogeneities.

MS. MS is displayed in Fig. 5. This parameter assesses the symmetry and reversibility of ventilation. Little or no difference between the V_p and the mode of the expired bolus (V_p  M_ex) indicates that the lung generally ventilates according to the first-in and last-out principle. A large difference (V_p < M_ex) suggests that ventilation is inhomogeneous and nonreversible. At each G level, the MS becomes more negative with increasing V_p. Up to a V_p of 600 ml, no significant differences were found among G levels. For larger V_p, the MS is more and more negative with increasing G and, therefore, with increasing ventilatory inhomogeneity. The increase in the MS may also be explained by a higher deposition at higher G levels. The particles that penetrate deeper into the lung deposit more, eroding the distal tail of the bolus and, therefore, shifting the mode of the expired bolus proximally. In µG, both deposition and ventilatory inhomogeneities are reduced, and the MS is greatly reduced.

Comparison with previous 1-G studies. The deposition, the dispersion, and the MS at 1 G were compared with data previously obtained by Brand et al. (4) and Darquenne et al. (7). Brand et al. (4) studied 79 healthy subjects and used V_p values ranging from 20 to 800 ml. Darquenne et al. (7) performed the bolus tests in 10 healthy subjects with V_p values ranging from 200 to 1,500 ml. The two previous studies used 0.87-µm-diameter particles and a flow rate of 0.25 l/s, compared with 1-µm-diameter particles and a flow rate of 0.45 l/s in our experiments. The three sets of data (means ± SD) for deposition, dispersion, and MS are displayed in Fig. 6, A-C, respectively. Given the differences in the protocols, our small subject population, and the intersubject and intrasubject variabilities, we found the values for all three parameters similar to those of other investigators. The deposition data shown in Fig. 6A are, however, higher than deposition obtained by Anderson et al. (2) and Kim et al. (13) for 1-µm-diameter particles.

View larger version (16K): [in this window] [in a new window]   Fig. 6.   Comparison of our 1-G data () with bolus studies of Brand et al. (4) () and Darquenne et al. (7) (). Data are means ± SD. In our study, particle size (dp) is 1 µm and flow rate () is 0.45 l/s. In Brand et al. (4) and Darquenne et al. (7) studies, dp is 0.87 µm and is 0.25 l/s. A: deposition, B: dispersion, C: mode shift.

Effect of changes in gas density caused by altitude. Several flights were performed to collect all the data. During each flight, before the start of the first parabola, we were able to collect data at 1 G and compare the measurements with those obtained on the ground in the same subject. The data are displayed in Fig. 7 for subject 2 used as an example. The comparison shows that the results obtained in both environments are similar, with no statistical differences between aircraft and ground data. This means that there were no systematic differences in our data introduced by the lower barometric pressure in the aircraft cabin and that we may, therefore, reliably compare aircraft and ground data. Similar comparisons were made for the three other subjects, and the results were the same.

View larger version (15K): [in this window] [in a new window]   Fig. 7.   Comparison between data obtained for subject 2 on the ground (, mean ± SD) and aboard the aircraft at 1 G (). A: deposition, B: dispersion, C: mode shift.

In summary, aerosol bolus inhalations were performed with 1-µm-diameter particles in four subjects on the ground and aboard the KC-135 aircraft during both weightlessness and the hypergravity phases. The boluses were inhaled at different V_p values ranging from 200 to 1,500 ml. The data showed that both bolus dispersion and deposition increased with V_p and that they were strongly G dependent, with the largest dispersion and deposition occurring for the largest G level. Even if dispersion was reduced in µG, it still increased steadily with V_p. The dispersion observed in µG can be explained by G-independent ventilatory inhomogeneities, the nonreversibility of the flows between inspiration, and expiration and cardiogenic mixing.