Aerosol transport and deposition in sequentially bifurcating airways

Deposition patterns and efficiencies of a dilute suspension of inhaled particles in three-dimensional double bifurcating airway models for both in-plane and 90 deg out-of-plane configurations have been numerically simulated assuming steady, laminar, constant-property air flow with symmetry about the first bifurcation. Particle diameters of 3, 5, and 7 microns were used in the simulation, while the inlet Stokes and Reynolds numbers varied from 0.037 to 0.23 and 500 to 2000, respectively. Comparisons between these results and experimental data based on the same geometric configuration showed good agreement. The overall trend of the particle deposition efficiency, i.e., an exponential increase with Stokes number, was somewhat similar for all bifurcations. However, the deposition efficiency of the first bifurcation was always larger than that of the second bifurcation, while in general the particle efficiency of the out-of-plane configuration was larger than that of the in-plane configuration. The local deposition patterns consistently showed that the majority of the deposition occurred in the carinal region. The distribution pattern in the first bifurcation for both configurations were symmetric about the carina, which was a direct result of the uniaxial flow at the inlet. The deposition patterns about the second carina showed increased asymmetry due to highly nonuniform flow generated by the first bifurcation and were extremely sensitive to bifurcation orientation. Based on the deposition variations between bifurcation levels and orientations, the use of single bifurcation models was determined to be inadequate to resolve the complex fluid-particle interactions that occur in multigenerational airways.     

Aerosol deposition in the lung with asymmetric airways obstruction: in vivo observation

Both the total and regional aerosol deposition were measured in six adult sheep before and after an induction of asymmetric airway obstructions, either by local instillation of carbachol solution (CS, 0.1%) distal to the right main bronchus or inhalation challenge of the right lung with carbachol aerosol (CA, 10 breaths). Total lung deposition was determined by monitoring inert monodisperse aerosols [1.0 micron mass median aerodynamic diam (MMAD)] breath-by-breath, at the mouth, by means of a laser aerosol photometer. Cumulative aerosol deposition over the first five breaths as a percent of the initial aerosol concentration (AD5) was used as a deposition index. Regional deposition pattern was determined by scintigraphic images of sulfur-colloid aerosol (1.5 microns MMAD) tagged with 99mTc. Radioactivity counts in the right (R) and left lung (L) were expressed as a percent of the whole lung count. Half-lung AD5 was then determined by multiplying AD5 by fractional radioaerosol depositions in R or L. Pulmonary airflow resistance (RL mean +/- SE), as determined by an esophageal balloon technique, increased by 111 +/- 28 and 250 +/- 96% after CA and CS, respectively (P less than 0.05). AD5 also increased in all the sheep tested by 29 +/- 3 and 52 +/- 8%, respectively, after CA and CS (P less than 0.05). Radioaerosol deposition pattern was even at base line (R/L = 51:49) but shifted toward the unchallenged L after CS (R/L = 40:60). Deposition pattern after CA was variable: a shift toward L in three, no change in one, and a shift toward the R lung in two sheep.(ABSTRACT TRUNCATED AT 250 WORDS)     

Particle deposition in obstructed airways

One approach to tackle the particle deposition in human lungs in close proximity is to develop an understanding of the particle motion in bifurcation airways. Chronic obstructive pulmonary disease (COPD) is one of the most common diseases in humans. COPD always results in inflammation that leads to narrowing and obstructing of the airways. The obstructive airways can alter the respiratory flow and particle deposition significantly. In order to study the effect of obstruction on particle deposition, four three-dimensional four-generation lung models based on the 23-generation model of Weibel [1963. Morphometry of the Human Lung. New York Academic Press, Springer, Berlin.] have been generated. The fully three-dimensional incompressible laminar Navier-Stokes equations are solved using computational fluid dynamics (CFD) solver on structured hexahedral meshes. Subsequently, a symmetric four-generation airway model serves as the reference and the other three models are considered to be obstructed at each generation, respectively. The calculation results show that the obstructive airway has significant influence on the particle deposition down-stream of the obstruction. The skewed velocity profile in the bifurcation airway is modified by the throat; consequently, more particles impact on the divider which results in higher deposition efficiency.     

Aerosol particle deposition in human lungs

The pneumoconiosis developing after inhalation of air-borne dusts in the work place depends on the relation between the value of particle deposition in the respiratory tract and the rate of particle clearance from sites of their deposition. For testing the deposition in humans an aerosol of paraffin oil was given to a cohort of healthy persons. The characteristic parameters of the aerosol had been defined. The concentration of particles in 5 channels were measured in both the inhaled and exhaled air samples using the particle counter ROYCO 225. The deposition fraction was calculated from the relation of particle amount in expired air to the amount in inhaled air in each distribution class. In this preliminary report the results comparable with the prediction mathematical curve are discussed.     

Platelet deposition onto fibrin-coated surfaces under flow conditions

Platelet deposition on fibrin-coated surfaces and release from these adherent platelets were studied in an in vitro flow system. When a mixed suspension of washed platelets and red cells flowed through a fibrin-coated glass tube, only platelets were deposited onto the fibrin-coated surfaces. The density of adhered platelets increased with flow time and decreased with distance from the tube inlet. The adhesion rate increased with increasing shear rates from 45 s-1 to 180 s-1. This adhesion process appears to fit a diffusion-limited mathematical model. Comparing with glass and other protein-coated surfaces such as collagen, fibrinogen, or albumin coated surfaces, the number of adhered platelet per unit area decreased in the following descending order: collagen, fibrin, fibrinogen, glass, albumin. On the other hand, the degree of release reaction from these platelets decreased by another order: collagen, glass, fibrinogen, fibrin. We observed little release from platelets that were in contact with a fibrin-coated surface. Our results suggest that platelets specifically adhere to fibrin-coated surface and that this interaction does not induce platelet release.     

Aerosol bolus dispersion in acinar airways--influence of gravity and airway asymmetry

The aerosol bolus technique can be used to estimate the degree of convective mixing in the lung; however, contributions of different lung compartments to measured dispersion cannot be differentiated unambiguously. To estimate dispersion in the distal lung, we studied the effect of gravity and airway asymmetry on the dispersion of 1 μm-diameter particle boluses in three-dimensional computational models of the lung periphery, ranging from a single alveolar sac to four-generation (g4) structures of bifurcating airways that deformed homogeneously during breathing. Boluses were introduced at the beginning of a 2-s inhalation, immediately followed by a 3-s exhalation. Dispersion was estimated by the half-width of the exhaled bolus. Dispersion was significantly affected by the spatial orientation of the models in normal gravity and was less in zero gravity than in normal gravity. Dispersion was strongly correlated with model volume in both normal and zero gravity. Predicted pulmonary dispersion based on a symmetric g4 acinar model was 391 ml and 238 ml under normal and zero gravity, respectively. These results accounted for a significant amount of dispersion measured experimentally. In zero gravity, predicted dispersion in a highly asymmetric model accounted for ～20% of that obtained in a symmetric model with comparable volume and number of alveolated branches, whereas normal gravity dispersions were comparable in both models. These results suggest that gravitational sedimentation and not geometrical asymmetry is the dominant factor in aerosol dispersion in the lung periphery.     

An implication of novel methodology to study pancreatic acinar mitochondria under in situ conditions

Mitochondria maintain numerous energy‐consuming processes in pancreatic acinar cells, yet characteristics of pancreatic mitochondrial oxidative phosphorylation in native conditions are poorly studied. Besides, it is not known which type of solution is most adequate to preserve functions of pancreatic mitochondria in situ. Here we propose a novel experimental protocol suitable for in situ analysis of pancreatic mitochondria metabolic states. Isolated rat pancreatic acini were permeabilized with low doses of digitonin. Different metabolic states of mitochondria were examined in KCl‐ and sucrose‐based solutions using Clark oxygen electrode. Respiration of digitonin‐treated, unlike of intact, acini was substantially intensified by succinate or mixture of pyruvate plus malate. Substrate‐stimulated respiration rate did not depend on solution composition. In sucrose‐based solution, oligomycin inhibited State 3 respiration at succinate oxidation by 65.4% and at pyruvate plus malate oxidation by 60.2%, whereas in KCl‐based solution, by 32.0% and 36.1%, respectively. Apparent respiratory control indices were considerably higher in sucrose‐based solution. Rotenone or thenoyltrifluoroacetone severely inhibited respiration, stimulated by pyruvate plus malate or succinate, respectively. This revealed low levels of non‐mitochondrial oxygen consumption of permeabilized acinar cells. These results suggest a stronger coupling between respiration and oxidative phosphorylation in sucrose‐based solution. Copyright © 2012 John Wiley & Sons, Ltd.     

A two-component theory of aerosol deposition in lung airways

The deposition of aerosol particles in the human lung airways is due to two distinct mechanisms. One is by direct deposition resulting from diffusion, sedimentation and impaction as the aerosol moves in and out of the lung. The other is an indirect mechanism by which particles are transported mechanically from the tidal air to the residential air and eventually captured by the airways due to intrinsic particle motion. This last mechanism is not well understood at present. Using a trumpet airway model constructed from Weibel's data, a two-component theory is developed. In this theory, the particle concentrations in the airways and the alveoli at a given airway depth are considered to be quantitatively different. This difference in concentrations will cause a net mixing between the tidal and residential aerosol as the aerosol is breathed in and out. A distribution parameter is then introduced to account for the distribution of ventilation. The effect of intrinsic particle motion on the aerosol mixing is also included. From this theory, total and regional deposition in the lung at the steady mouth breathing without pause is calculated for several different respiratory cycles. The results agree reasonably well with the experimental data.     

Ion transport by sheep distal airways in a miniature chamber

Ion transport and the electric profile of distal airways of sheep lungs were studied in a miniature polypropylene chamber with a 1-mm aperture. Small airways with an inner diameter < 1 mm were isolated, opened longitudinally, and then mounted as a flat sheet onto the 1-mm aperture where it was glued and secured with an O-ring. Both sides of the tissue were bathed with identical physiological solutions at 37 degrees C and oxygenated. Pooled data from 27 distal airways showed an inner airway diameter of 854 +/- 22 (SE) microm and a transepithelial potential difference (PD) of 1.86 +/- 0.29 mV, lumen negative. Short-circuit current (I(sc)) was 25 +/- 3.5 microA/cm(2), tissue resistance was 96 +/- 14 Omega, and conductance was 15.2 +/- 1.7 mS/cm(2). At baseline, amiloride-sensitive Na transport accounted for 51% of I(sc) (change in I(sc) = 9.7 +/- 2.6 microA/cm(2); n = 8 airways), corresponding to 0.36 microeq. cm(-2). h(-1). Treatment with 0.1 mM bumetanide did not reduce the I(sc) (n = 5 airways). Exposure to 1 microM Ca ionophore A-23187 raised the I(sc) by 9 microA/cm(2) (47%; P < 0.03; n = 6 airways). The latter effect was blunted by bumetanide. Carbachol at 1 microM provoked a biphasic response, an initial rapid rise in I(sc) followed by a decline (n = 3 airways). There was no significant increase in PD or I(sc) in response to isoproterenol or dibutyryl cAMP. The data suggest that Na absorption constitutes at least 50% of baseline transport activity. Cl or other anion secretion such as HCO(3) appears to be present and could be stimulated by raising intracellular Ca.     

Strain shielding in distal femur after patellofemoral arthroplasty under different activity conditions

Strain shielding, a mechanical effect occurring in structures combining stiff with more flexible materials, is considered to lead to a reduction of density in bone surrounding the implant. This effect can be related to the weakness of the implant fixation, which can promote implant loosening. Several studies describe a significant decrease in postoperative bone mineral density adjacent to joint implants, which can compromise their long-term fixation. The aim of the present study was to quantify the strain shielding effect on the distal femur after patellofemoral arthroplasty. For this purpose three activities of daily living were considered: level walking, stair climbing and deep bending at different angles of knee flexion. To determine the strain shielding effect, cortical bone strains were measured experimentally with triaxial strain gauges in synthetic femurs before and after patellofemoral arthroplasty for each of the different daily activities. The results showed that the patellofemoral arthroplasty in general reduced the strains in the medial and distal regions of the femur when deep bending activity occurred, consequently, strain shielding in these regions, with strain decreases of ?72.0% and ?67.5% were measured. On the other side, higher values of strain were found in the anterior region after patellofemoral replacement for this activity with an increase of +182.0%. The occurrence of strain shielding seems to be more significant when the angle of knee flexion and applied load increases. Strain shielding and over-loading may have relevant effects on bone remodeling surrounding the patellofemoral implant, suggesting a potential effect of later bone resorption in the medial and distal femur regions in case of regular deep bending activity.     

Morphometrical and immunocytochemical studies on rat pancreatic acinar cells under control and experimental conditions

Process of amylase and chymotrypsinogen secretion by acinar cells has been studied applying morphological and biochemical approaches. Three conditions were investigated; resting (fed control), cholinergic stimulation and fasting. Morphometrical evaluations have shown that under stimulation, the volume density of zymogen granules decreases drastically while that of the Golgi apparatus increases. This may result from the enhancement in protein processing and the rapid discharge. Quantitation of amylase and chymotrypsinogen immunolabelings present over the cellular compartments has shown that there is no difference in the intensities between tissues from control and stimulated animals. These results imply that total amounts of protein processed by the Golgi apparatus are markedly enhanced primarily because of the increase in size of the organelle, the amounts of protein processed per unit surface remaining unchanged. Under starvation where reduction of secretion occurs, there is a significant decrease in the volume density of the Golgi apparatus but no variation in that of the zymogen granules. However, the morphological aspect of these was markedly altered since many of them present an electron luscent periphery which was devoid of immunolabeling for amylase and chymotrypsinogen. Quantitation of amylase and chymotrypsinogen immunolabelings has shown significant diminution for both enzymes. In both experimental conditions, the volume density of lysosomes was enhanced, however in none of these conditions evidence of crinophagy was observed. The morphometrical and immunocytochemical results were consistent with those obtained from biochemical determination of amylase and chymotrypsinogen contents in tissues. Correlations between results obtained from morphometric and immunocytochemical studies were made leading to a better understanding of the cellular secretory activity during experimental conditions.     

Computational modeling and validation of human nasal airflow under various breathing conditions

The human nose serves vital physiological functions, including warming, filtration, humidification, and olfaction. These functions are based on transport phenomena that depend on nasal airflow patterns and turbulence. Accurate prediction of these airflow properties requires careful selection of computational fluid dynamics models and rigorous validation. The validation studies in the past have been limited by poor representations of the complex nasal geometry, lack of detailed airflow comparisons, and restricted ranges of flow rate. The objective of this study is to validate various numerical methods based on an anatomically accurate nasal model against published experimentally measured data under breathing flow rates from 180 to 1100 ml/s. The numerical results of velocity profiles and turbulence intensities were obtained using the laminar model, four widely used Reynolds-averaged Navier-Stokes (RANS) turbulence models (i.e., k-ε, standard k-ω, Shear Stress Transport k-ω, and Reynolds Stress Model), large eddy simulation (LES) model, and direct numerical simulation (DNS). It was found that, despite certain irregularity in the flow field, the laminar model achieved good agreement with experimental results under restful breathing condition (180 ml/s) and performed better than the RANS models. As the breathing flow rate increased, the RANS models achieved more accurate predictions but still performed worse than LES and DNS. As expected, LES and DNS can provide accurate predictions of the nasal airflow under all flow conditions but have an approximately 100-fold higher computational cost. Among all the RANS models tested, the standard k-ω model agrees most closely with the experimental values in terms of velocity profile and turbulence intensity.     

Scaffolds for engineering smooth muscle under cyclic mechanical strain conditions

Cyclic mechanical strain has been demonstrated to enhance the development and function of engineered smooth muscle (SM) tissues, but appropriate scaffolds for engineering tissues under conditions of cyclic strain are currently lacking. These scaffolds must display elastic behavior, and be capable of inducing an appropriate smooth muscle cell (SMC) phenotype in response to mechanical signals. In this study, we have characterized several scaffold types commonly utilized in tissue engineering applications in order to select scaffolds that exhibit elastic properties under appropriate cyclic strain conditions. The ability of the scaffolds to promote an appropriate SMC phenotype in engineered SM tissues under cyclic strain conditions was subsequently analyzed. Poly(L-lactic acid)-bonded polyglycolide fiber-based scaffolds and type I collagen sponges exhibited partially elastic mechanical properties under cyclic strain conditions, although the synthetic polymer scaffolds demonstrated significant permanent deformation after extended times of cyclic strain application. SM tissues engineered with type I collagen sponges subjected to cyclic strain were found to contain more elastin than control tissues, and the SMCs in these tissues exhibited a contractile phenotype. In contrast, SMCs in control tissues exhibited a structure more consistent with the nondifferentiated, synthetic phenotype. These studies indicate the appropriate choice of a scaffold for engineering tissues in a mechanically dynamic environment is dependent on the time frame of the mechanical stimulation, and elastic scaffolds allow for mechanically directed control of cell phenotype in engineered tissues.     

Aerosol deposition and flow limitation in a compliant tube

Studies in intact dogs have suggested that aerosol deposition is enhanced in the proximity of a flow-limiting segment (FLS) formed during cough. The mechanism for that observation was investigated using a monodisperse (geometric SD less than or equal to 1.15) fluorescent aerosol produced in a condensation generator. The aerosol was passed through a compliant tube (Penrose) that had been mounted vertically in a two-chamber box. The surrounding pressure (Ps) in the upstream chamber was controlled independent of the surrounding pressure in the downstream chamber, thus allowing development of an FLS near the exit of the upstream chamber. At fixed inlet pressure (P1) and Ps, flow limitation was achieved over a range of 0.1-0.5 l X s-1 by lowering downstream pressure alone (P2). The influence of the FLS cross-sectional geometry on the site of peak deposition was examined because area of an FLS is a function of transmural pressure (Ptm = Px - Ps). For those constriction geometries that did not involve opposing wall contact, the deposition distribution was characterized by a single peak immediately downstream of the constriction. In the most compressed geometries the peak in deposition was diminished and shifted further downstream. Total aerosol deposition was found to be characterized by a dimensionless particle inertia parameter formed as the ratio of particle stopping distance and the minor radius of the elliptical tube cross section. The deposition of small particles with an inertial parameter less than 0.01 was found to be independent of geometry and constriction velocity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevated levels of NO are localized to distal airways in asthma

The contribution of nitric oxide (NO) to the pathophysiology of asthma remains incompletely defined despite its established pro- and anti-inflammatory effects. Induction of the inducible nitric oxide synthase (iNOS), arginase, and superoxide pathways is correlated with increased airway hyperresponsiveness in asthmatic subjects. To determine the contributions of these pathways in proximal and distal airways, we compared bronchial wash (BW) to traditional bronchoalveolar lavage (BAL) for measurements of reactive nitrogen/oxygen species, arginase activation, and cytokine/chemokine levels in asthmatic and normal subjects. Levels of NO were preferentially elevated in the BAL, demonstrating higher level NOS activation in the distal airway compartment of asthmatic subjects. In contrast, DHE(+) cells, which have the potential to generate reactive oxygen species, were increased in both proximal and distal airway compartments of asthmatics compared to controls. Different patterns of cytokines and chemokines were observed, with a predominance of epithelial cell-associated mediators in the BW compared to macrophage/monocyte-derived mediators in the BAL of asthmatic subjects. Our study demonstrates differential production of reactive species and soluble mediators within the distal airways compared to the proximal airways in asthma. These results indicate that cellular mechanisms are activated in the distal airways of asthmatics and must be considered in the development of therapeutic strategies for this chronic inflammatory disorder.     

氮沉降和刈割条件下羊草光响应模型比较及响应特性

草地覆盖全球陆地面积的40%左右,在全球碳循环中发挥着重要作用。近年来,人类活动,如化石燃料燃烧和畜牧业的发展显著增加了氮在全球环境中的沉积。草地管理方式（如刈割）在介导氮沉降对草地植物的影响方面具有重要作用。因此,筛选合适的模型对光响应过程进行拟合并计算相关参数对研究植物光合特性具有重要意义。依托6种氮添加（NH₄NO₃）梯度和两种草原管理方式（刈割和不刈割）交互处理的野外控制实验,利用Li-6400便携式光合作用系统测定上述实验平台的优势种羊草（Leymus chinensis）的光合作用-光响应过程。采用直角双曲线模型、非直角双曲线模型、指数模型和直角双曲线修正模型4种光响应模型对羊草光响应曲线进行拟合,从参数拟合效果和模型拟合优度筛选氮添加和刈割条件下羊草的最佳拟合模型并分析羊草的光合特性。结果表明：指数模型对表观量子效率（α）、光饱和点（LSP）和最大净光合速率（P_nmax）具有较好的参数拟合效果,非直角双曲线模型的模型拟合优度最好。在所有处理中,羊草均未表现出明显的光抑制现象,具有一定的光合潜力和适应环境变化的能力。适度氮添加和刈割处理能提高羊草净光合速率（P_n）、气孔导度（G_s）、P_nmax、α和LSP等,提升了羊草的光能利用率并拓宽了光强利用范围,但过度氮添加并不能进一步提高光合能力。综上,指数模型和非直角双曲线模型较适用于氮添加和刈割条件下羊草的光响应曲线拟合,施氮浓度为20 g N m^-2 a^-1并刈割是最有利于提高羊草光合能力的草原管理措施。探讨了不同氮添加浓度和刈割处理对优势种羊草的交互影响,从光合作用角度分析羊草的适应机制,将对未来全球氮沉降增加情况下的草地管理方案提供科学依据。