Deposition and dispersion of 1-micrometer aerosol boluses in the human lung: effect of micro- and hypergravity

We performed bolus inhalations of 1-micrometer particles in four subjects on the ground (1 G) and during parabolic flights both in microgravity (microG) and in approximately 1.6 G. Boluses of approximately 70 ml were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 200 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The deposition, dispersion, and position of the bolus in the expired gas were calculated from these data. For Vp >/=400 ml, both deposition and dispersion increased with Vp and were strongly gravity dependent, with the greatest deposition and dispersion occurring for the largest G level. At Vp = 800 ml, deposition and dispersion increased from 33.9% and 319 ml in microG to 56.9% and 573 ml at approximately 1.6 G, respectively (P < 0.05). At each G level, the bolus was expired at a smaller volume than Vp, and this volume became smaller with increasing Vp. Although dispersion was lower in microG than in 1 G and approximately 1.6 G, it still increased steadily with increasing Vp, showing that nongravitational ventilatory inhomogeneity is partly responsible for dispersion in the human lung.     

Experimental measurements and empirical modelling of the regional deposition of inhaled particles in humans

Regional deposition of inhaled particles was studied experimentally in a hollow cast of the human larynx-tracheobronchial tree extending through the first six branching levels, and in twenty-six non-smoker human volunteers in vivo. Results of the hollow cast study indicated a linear dependence of particle deposition efficiency on the Stokes number for aerosols with aerodynamic diameters greater than 2 micrometers. Alveolar and total respiratory tract in vitro deposition in healthy non-smokers was minimal for particles of approximately 0.4 micrometers, and alveolar deposition for mouthpieces inhalations peaked for particles of approximately 3 micrometers. A new anatomic parameter, the bronchial deposition size (BDS), is introduced to permit the classification of various individuals and populations according to their tracheobronchial deposition efficiencies. The average BDS's were 1.20 cm for 26 healthy non-smokers, 1.02 cm for 46 cigarette smokers, 0.90 cm for 19 clinical patients being treated for obstructive lung disease and 0.60 cm for six severely disabled patients.     

Regional deposition of inhaled particles in human lungs: comparison between men and women

We measured detailed regional deposition patterns of inhaled particles in healthy adult male (n = 11; 25 +/- 4 yr of age) and female (n = 11; 25 +/- 3 yr of age) subjects by means of a serial bolus aerosol delivery technique for monodisperse fine [particle diameter (Dp) = 1 micron] and coarse aerosols (Dp = 3 and 5 micron). The bolus aerosol (40 ml half-width) was delivered to a specific volumetric depth (Vp) of the lung ranging from 100 to 500 ml with a 50-ml increment, and local deposition fraction (LDF) was assessed for each of the 10 local volumetric regions. In all subjects, the deposition distribution pattern was very uneven with respect to Vp, showing characteristic unimodal curves with respect to particle size and flow rate. However, the unevenness was more pronounced in women. LDF tended to be greater in all regions of the lung in women than in men for Dp = 1 micron. For Dp = 3 and 5 micron, LDF showed a marked enhancement in the shallow region of Vp 200 ml. Total lung deposition was comparable between men and women for fine particles but was consistently greater in women than men for coarse particles regardless of flow rates used: the difference ranged from 9 to 31% and was greater with higher flow rates (P < 0.05). The results indicate that 1) particle deposition characteristics differ between healthy men and women under controlled breathing conditions and 2) deposition in women is greater than that in men.     

Use of aerosols to estimate pulmonary air-space dimensions

Single-breath inhalations of monodisperse aerosols were performed with a group of normal subjects to determine aerosol recovery from the human lung after periods of breath holding. Aerosols of monodisperse nonhygroscopic droplets of bis(2-ethylhexyl) sebacate of between 0.5 and about 2.5 micron diam were used for the inhalation. The inhalation apparatus allows continuous monitoring of particle number concentration and flow rate close to the mouth. Experiments were designed to find the optimum experimental conditions for the principal concept of Palmes et al (In: Inhaled Particles and Vapours. London: Pergamon, 1976, vol. II. p. 339-347) to evaluate pulmonary air-space dimensions by means of aerosols. The experimental results obtained for various respiratory flow rates (125, 250, and 500 cm3 X s-1), settling velocities of the particles (10(-3) to 1.5 X 10(-2) cm X s-1) and volumes of inspired aerosols (500, 1,000, and 2,000 cm3) are compared with the results derived from a mathematical model for the particle deposition during respiratory pauses. Monodisperse aerosols with particles between 1 and about 1.5 micron diam. inspired for breath holding into the lung region of interest, may provide optimum conditions for the sizing of air spaces by means of aerosols.     

Effect of lung function and mode of inhalation on penetration of aerosol into the human lung

The method using radioactive tracer particles has been applied to study the effect of the mode of inhalation of aerosols on the depth of deposition in the lungs of 50 patients with airways obstruction. The findings show that the penetration of particles is directly related to: (1) volume inspired per breath (VI); (2) forced expiratory volume in one second (FEV1); and inversely related to (3) flow rate during inhalation (V). In mathematical terms, alveolar deposition (%) = 40-3 (VI)+10-98 (FEV1)--0-75 (V)+40-4; for this regression F = 4-41 and P less than 0-01.     

Cardiogenic oscillation phase relationships during single-breath tests performed in microgravity

We studied the phase relationships of the cardiogenic oscillations in the phase III portion of single-breath washouts (SBW) in normal gravity (1 G) and in sustained microgravity (microG). The SBW consisted of a vital capacity inspiration of 5% He-1.25% sulfurhexafluoride-balance O2, preceded at residual volume by a 150-ml Ar bolus. Pairs of gas signals, all of which still showed cardiogenic oscillations, were cross-correlated, and their phase difference was expressed as an angle. Phase relationships between inspired gases (e.g., He) and resident gas (n2) showed no change from 1 G (211 +/- 9 degrees) to microG (163 +/- 7 degrees). Ar bolus and He were unaltered between 1 G (173 +/- 15 degrees) and microG (211 +/- 25 degrees), showing that airway closure in microG remains in regions of high specific ventilation and suggesting that airway closure results from lung regions reaching low regional volume near residual volume. In contrast, CO2 reversed phase with He between 1 G (332 +/- 6 degrees) and microG (263 +/- 27 degrees), strongly suggesting that, in microG, areas of high ventilation are associated with high ventilation-perfusion ratio (VA/Q). This widening of the range of VA/Q in microG may explain previous measurements (G.K. Prisk, A.R. Elliott, H.J.B. Guy, J.M. Kosonen, and J.B. West J. Appl. Physiol. 79: 1290-1298, 1995) of an overall unaltered range of VA/Q in microG, despite more homogeneous distributions of both ventilation and perfusion.     

Atrial distension in humans during microgravity induced by parabolic flights

The hypothesis was tested that human cardiac filling pressures increase and the left atrium is distended during 20-s periods of microgravity (microG) created by parabolic flights, compared with values of the 1-G supine position. Left atrial diameter (n = 8, echocardiography) increased significantly during microG from 26.8 +/- 1.2 to 30.4 +/- 0.7 mm (P < 0.05). Simultaneously, central venous pressure (CVP; n = 6, transducer-tipped catheter) decreased from 5.8 +/- 1.5 to 4.5 +/- 1.1 mmHg (P < 0.05), and esophageal pressure (EP; n = 6) decreased from 1.5 +/- 1.6 to -4.1 +/- 1.7 mmHg (P < 0.05). Thus transmural CVP (TCVP = CVP - EP; n = 4) increased during microG from 6.1 +/- 3. 2 to 10.4 +/- 2.7 mmHg (P < 0.05). It is concluded that short periods of microG during parabolic flights induce an increase in TCVP and left atrial diameter in humans, compared with the results obtained in the 1-G horizontal supine position, despite a decrease in CVP.     

Human papillomavirus infection in women. Special aspects of infectious diseases in women

These studies assess the quantity and morphology of the emitted aerosolized dose of irregularly shaped disodium cromoglycate particles in the fine particle fraction using in vitro methods. Disodium cromoglycate was treated with a homologous series of saturated fatty acids, between C8 and C18, in a range of concentrations. The products of these treatments were powders with a variety of particle size, shape, and aggregation characteristics. Samples of these powders were loaded in gelatin capsules, generated as aerosols from a Rotahaler and collected in a two-stage liquid impinger or eight-stage inertial impactor. Particles were examined directly by scanning electron microscopy and subsequently the images were analyzed to define morphology. The aerodynamic fine-particle fraction determined by the two-stage impinger increased approximately twofold with lauric acid treatment (0.0317 g/g, 6.7%) and threefold with stearic acid treatment (0.58 g/g; 9.7%) compared with disodium cromoglycate alone (0 g/g, 3.56%). The lauric acid formulation appeared to alter deposition primarily by changing particle morphology. Stearic acid altered particle shape to some extent and the increase in the fine-particle fraction appeared to be attributable to improved particle dispersion properties. The uncontrolled presence of irregular-shaped particles can introduce dosing errors due to effects on dispersion and aerodynamic behavior. Conversely, controlled particle morphology and size may be employed to optimize the dose delivered to the lungs particularly if particle-particle and particle-surface interactions can be minimized.     

Study of inclusion re-entrainment in a filter bed

Filtration is widely used in various processes such as water treatment and aluminum casting for the removal of unwanted impurities called inclusions. The deposited inclusions can re-enter the flow as a result of the unfavorable hydrodynamic conditions within the system or flow instabilities, such as flow stop/start periods during casting cycles in the aluminum industry. In this project, the re-entrainment of inclusions was studied as a function of filter-bed length, particle size, inlet inclusion concentration, and inlet velocity. A physical model using water containing PVC particles as inclusions was built. Experiments were carried out under continuous-flow as well as interrupted-flow conditions in this pilot-scale filter. It was found that the smaller bed particles and longer bed length enhance the deposition and reduce the re-entrainment of inclusions. Increasing the inlet velocity has a negative effect on the deposition and increases the re-entrainment. A one-dimensional mathematical filtration model has also been developed, and its predictions were compared with the experimental data from the pilot filter and the plant. This article presents the experimental study, its results, and the comparison between model predictions and experimental data. Applicability of the model to aluminum filtration is also illustrated.     

Retention of insoluble particles after local intrabronchial deposition in dogs

Recent studies have challenged the generally accepted hypothesis that bronchial particle clearance is complete within 24-48 h postdeposition. We studied bronchial retention of inert particles using a bronchoscope and microspray nozzle to localize deposition in a bronchus while avoiding alveolar deposition. Six-microliter aliquots (444 kBq) of submicrometer (number mean diameter = 0.22 microns, geometric standard deviation = 1.75) technetium-99m-labeled (99mTc) sulfur colloid (SC) particles (n = 6) or the unbound radiolabel 99mTc-pertechnetate (99mTcO4-; n = 3) were sprayed onto a 5-mm-diam bronchus in halothane-anesthetized dogs. Radioactivity at the deposition site and clearance pathway was monitored externally with a gamma camera beginning immediately postspray. Bronchial retention of SC was 8.5 +/- 2.4 and 1.5 +/- 0.7% at 3 and 24 h postspray, respectively. Tracheal mucus velocity was measured at 10.4 +/- 2.2 mm/min. For comparison, clearance of inhaled submicrometer SC particles was also measured in the same dogs. Retention of inhaled aerosolized SC (peripheral lung deposition) was 98.1 +/- 1.1 and 76.3 +/- 1.8% at 3 and 24 h, respectively. 99mTcO4- cleared from the bronchi slightly more rapidly than did SC. Radioactivity was readily detected in the blood after deposition of 99mTcO4- but not of SC. Thus SC cleared by mucociliary transport, whereas 99mTcO4- cleared predominantly by transepithelial absorption. We conclude that clearance of submicrometer particles from a 5-mm conducting airway is very nearly complete by 24 h, with approximately 92% of the clearance occurring within the first 3 h postdeposition.     

Fractionation and Segregation of Suspended Particles Using Acoustic and Flow Fields

The exploratory research of applying an acoustic standing wave to a sediment flow stream to fractionate and segregate particles was investigated. Using fundamental physics of particles in an acoustic field, a mathematical model was developed to calculate trajectories of deflected particles due to the application of acoustic standing waves. Then at the bench scale, the above technology was implemented by building a flow chamber with two transducers at opposite ends to generate an acoustic standing wave. The technology was evaluated using uniform size silicon dioxide and silicon carbide particle suspensions in de-ionized water. Due to the acoustic force field, SiO2 particles migrated toward the pressure nodes at half wavelength intervals at an optimum frequency of 333 kHz and 40 W power. Dark lines representing particle columns were formed after the application of the acoustic field, which was recorded in videotape. However, due to the small particle size of SiO2, particle trajectories could not be recorded, hence the slightly larger sized SiC was used to track particle trajectories. The displacements of SiC particles due to an acoustic force were compared with the mathematical model predictions. For input power level between 3.0 and 5.0 W, the experimental data were comparable to mathematical model predictions. Also, from the experimental data it was possible to develop a relationship between input power and acoustic energy in the resonance chamber. Hence based on preliminary results it can be concluded that the acoustic field can be used either to segregate or fractionate fine particles.     

Mechanistic insights derived from retardation and peak broadening of particles up to 200 nm in diameter in electrophoresis in semidilute polyacrylamide solutions

Rigid spherical particles in the size range of 5-200 nm diameter were subjected to capillary zone electrophoresis (CZE) in semidilute solutions of uncross-linked polyacrylamide of M(r) 5, 7 and 18 x 10(6) (PA-5, -7 and -18, respectively) of varying concentrations up to 1.6% and at field strengths varying from 68 to 270 V/cm. For all particles under study, the experimental Ferguson plots, log(mobility) vs. polymer concentration, permit a linear approximation. Their slope, the retardation coefficient KR = delta log (mobility)/delta (concentration), for particles smaller than 30 nm in diameter increased with particle size in PA-5 and -7 independently of electric field strength and polymer M(r). The KR of particles of 30 nm in diameter or more was found to be independent of particle size at the lowest field strength used but to decrease with it at the higher values of field strength. The decrease was parallel but shifted to higher values of retardation when the polymer M(r) increased from 5 to 7 x 10(6). With a decreasing ratio of average mesh size of the polymer network, zeta, to particle radius, R, the approach to "continuity" of the polymeric medium (zeta/R < 1) with both increasing particle size and polymer concentration does not result in the retardation behavior expected according to the macroscopic (bulk) viscosity of the solution. These experimental observations were hypothetically interpreted in terms of a transition to a retardation mechanism comprising the formation of a polymer depletion layer near the particle surface--polymer solution interface. Peak width exhibited an overall increase with PA-7 concentration for all particles studied. For particles of 30 nm in diameter or less, the increase was steepest when the radius of the particle was approximately commensurate with zeta at a given polymer concentration. For the largest particle, 205 nm in diameter, peak broadening with polymer concentration was found to correlate linearly with peak asymmetry. CZE of the particles in PA-18 solutions revealed abnormal behavior, with both mobility and peak width remaining near-constant up to a concentration of 0.08% and sharply declining at higher concentrations. The decline of relative mobility is the same-for the entire particle size range used, while peak width declines in direct relation to particle size.     

Particle Size and Clogging of Granular Media Permeated with Leachate

The effect of particle size (4-, 6-, and 15-mm nominal sizes) on the rate of clogging of columns of porous media permeated with municipal solid-waste leachate is examined. Clogging is shown to be more localized over a small volume of the porous media near the influent end of the column for smaller particles than for larger particles, where clogging was more uniformly distributed along the column. This is attributed to the greater surface area per unit volume of smaller particles allowing greater biofilm growth per unit volume. This increased the reduction in chemical oxygen demand (COD) and caused greater deposition of inorganic clog material per unit length of column than for larger particles. The distribution of methanogenic bacteria was found to closely correspond to the zones of most severe clogging. The bulk density of clog material is shown to be between 1.6 and 1.8 Mg∕m3. The chemical composition of the clog material is essentially independent of particle size, with calcium representing 26% of the dry mass of the clog material and CaCO3 being the main component of the clog. An examination of the yield of CaCO3 relative to COD indicates that the carbon in the CaCO3 represents <4% of the organic carbon represented by the drop in COD. Finally, the data from the column test is used to predict the expected time to clog for an actual landfill and were found to give results consistent with what was observed in the field.     

Lidocaine-loaded biodegradable nanospheres. I. Optimization Of the drug incorporation into the polymer matrix

Spherical nanoparticulate drug carriers made of poly(d,l-lactic acid) with controlled size were designed. A local anesthetic, lidocaine, a small hydrophobic molecule, was incorporated in the core with loadings varying from about 7 to 32% (w/w) and increasing with the particle size. Particles with sizes from about 250 to 820 nm and low polydispersity were prepared with good reproducibility; the polymer concentration (at constant surfactant concentration) governed the particle size. The large particles with a high loading ( approximately 30%) showed under in vitro conditions a slow release over 24-30 h, the medium sized carriers (loading of approximately 13%) released the drug over about 15 h, whereas the small particles with small loading ( approximately 7%) exhibited a rapid release over a couple of hours. It seems that the drug release rate is related to the state (crystallized or dispersed) of the drug incorporated in the polymer matrix.     

Controlled dissolution from wax-coated aerosol particles in canine lungs

Treatment of pulmonary and systemic diseases may be improved and toxicity reduced by pulmonary deposition of drug-containing aerosols exhibiting delayed dissolution. Aqueous disodium fluorescein and pentamidine aerosols were dried, concentrated, and condensation coated with paraffin wax. The apparent mass median aerodynamic diameters of the coated fluorescein particles were 2.8-4.0 microns. Wax-to-fluorescein ratios were 0.38-1.05. The dissolution half times determined using a single-pass flow system were 1.5 min for uncoated fluorescein and 0.8 min for uncoated pentamidine. These increased over threefold when the aerosols were coated with paraffin wax to maxima of 5.3 and 2.6 min, respectively. Wax-coated aerosols generated from fluorescein mixed with 99mTc-labeled iron oxide colloid delivered to the canine lungs demonstrated a 3.4-fold increase in the absorption half time of disodium fluorescein compared with uncoated fluorescein (11.2 vs. 38.4 min). The absence of changes in pulmonary function on inhalation of these wax-coated aerosols, together with a high drug load and delayed release, establishes a foundation for future therapeutic applications.     

喷射成型Zn60Al32Cu2Si6过喷粉末的研究

通过喷射成型技术制备了Zn60A132Cu2Si6合金粉末,并通过X射线衍射、扫描电镜及激光粒度仪对粉末的物相能成、微观形貌和粒度分布进行了分析.结果显示:粉末由富Al的а相、富zn的η相、Si相以及少量的富铜相ε-CuZn4组成,粉末形貌大部分为圆球形,且有卫星颗粒,粉末尺寸分布在2～40gμm之间.     

Effect of antibiotic growth promoters and anticoccidials on growth of Clostridium perfringens in the caeca and on performance of broiler chickens

The purpose of this study was to analyze atomizer performance in the production of respirable spray-dried particles. An ultrasonic nebulizer and a plain-jet airblast atomizer were evaluated in an open cycle, cocurrent spray-drying tower using a 0.5% w/v disodium fluorescein solution. The plain-jet airblast atomizer produced smaller initial droplet sizes (D32 = 4.5-4.8 microns) relative to the ultrasonic nebulizer (D32 = 20-48 microns) over a range of atomizer operating conditions. The airblast atomizer was selected for further analysis in two spray-drying tower configurations: grounded and electrostatically charged. The spray-dried particles produced by the airblast atomizer were of a size range (mass median aerodynamic diameter [MMAD] < 1.6 microns) suitable for inhalation. Significant differences were observed for the grounded and electrostatically charged tower configurations, the latter producing the smaller median particle size at the expense of decreased collection efficiency. The electrostatically charged tower was size selective because of diffusion charging, retaining particles with an aerodynamic diameter (Dae) in the range 1 < Dae < 2 microns. The particle size was reduced with decreasing ambient relative humidity, although a controlled study of this parameter would be required to explicitly define its effects.     

离子型稀土矿土壤粒度分布特征研究——以赣县姜窝子稀土矿山为例

颗粒粒度分布对土壤水分运动和溶质迁移,以及水土流失有重要影响. 利用水洗分筛和激光粒度分析技术研究了江西赣县姜窝子稀土矿土壤颗粒粒度并探讨了土壤颗粒粒度在垂直方向的分布规律. 研究表明,姜窝子稀土矿山土壤颗粒粒度分布受风化程度、颗粒垂向迁移因素的影响,呈如下分布:①离子型稀土矿土壤颗粒按直径分为粗、细、粉、黏粒结构,且土壤粗颗粒以石英为主,稀土矿土壤颗粒粒度呈驼峰式分布,即粒径在粗颗粒（ > 2 mm） 和黏粒（ < 0.075 mm）含量较高,粒径在细、粉粒（0.075~2 mm）含量相对较低;②受风化程度和颗粒垂向迁移的影响,稀土矿土壤细、黏粒组分的含量随深度增大呈先升后降的曲线形态;③黏粒（ < 0.075 mm）激光粒度分析表明,颗粒分布随粒径的大小变化与粒径大于0.075 mm的颗粒在深度上的分布相似.      

Effect of Adsorbent Particle Layering on Performance of Conventional and Tapered Fixed-Bed Adsorbers

Experimental and modeling studies were conducted for the adsorption of phenol from aqueous solutions onto activated carbon in fixed beds with the adsorbent particles layered according to particle size. In the conventional stratified cylindrical adsorber (SCA), the particles were layered according to natural stratification, and increased in size with column depth. In the reverse stratified tapered adsorber (RSTA), the particle size decreased with column depth, and the fluid velocity decreased in the direction of flow. Experimental data indicate that for a uniform particle size distribution, the breakthrough time for the RSTA was about 60% higher than for the SCA under identical carbon loading and flow conditions. The homogeneous solid phase diffusion model with Linear-Freundlich isotherm was used to model the layered adsorbers. It provides excellent predictions for breakthrough curves at various column depths. Bed capacity utilization can be increased with the RSTA due to the sharpening of the solute front, and this will translate into lower capital and operating costs for the carbon adsorption system due to the smaller unit required, lower carbon inventory, and lower pumping costs.