Aerosol Bolus Dispersion Research Articles

Aerosol bolus dispersion in patients with bronchiolitis obliterans after heart-lung and double-lung transplantation. The Munich Lung Transplantation Group.

Bronchiolitis obliterans (BO) is one of the main late complications in patients after lung transplantation. Because BO is located in small airways, conventional lung function tests are supposed to be rather insensitive to detect early stages of this disease. In this study, the capability of the aerosol bolus dispersion test to detect BO was tested in 12 subjects with heart-lung and double-lung transplantation. Four of these patients had histological evidence of BO. The broadening (dispersion) of inhaled boluses consisting of monodispersed inert test particles during respiration was repeatedly measured in each subject. Additional measurements of spirometric and bodyplethysmographic measurements were performed. Patients with evidence of BO showed significantly increased aerosol bolus dispersion and significantly reduced maximal airflow parameters. Calculation of receiver operating characteristics (ROCs) revealed that from all lung function parameters under consideration, aerosol bolus dispersion divided by the maximum expiratory flow rate at 50% of vital capacity (MEF50) and MEI50 had the highest sensitivity and specificity for the detection of BO. Both parameters showed a sensitivity and specificity of 100%. Therefore, it may be speculated that even in early stages of disease, the combination of MEF50 measurement with aerosol bolus dispersion measurements may be a powerful tool for the detection of BO in patients with lung transplantation.

Aerosol bolus dispersion in healthy subjects.

Aerosol bolus dispersion is a physiological test of lungs, which uses monodisperse submicron particles to measure intrapulmonary convective gas mixing. In this study, aerosol bolus dispersion was measured in healthy subjects in order to assess reference values for possible clinical applications, to assess the reproducibility of these values, and to identify physical and physiological factors influencing aerosol bolus dispersion. Aerosol bolus dispersion was measured in 79 healthy subjects using 20 cm3 aerosol boluses consisting of monodisperse di-2-ethylhexyl sebacate (DEHS) particles. The reproducibility of parameters characterizing the width of the exhaled bolus was of the same order as that of parameters of the flow-volume curve (10%). Aerosol bolus dispersion was independent of the level of lung inflation, and the slope of the relationship between flow rate and dispersion was on average not significantly different from zero (range 100-700 cm3.s-1). Multiple linear regression showed that aerosol bolus dispersion increased with increasing total lung capacity of the subject. We conclude that differences in total lung capacity between individuals should be taken into account when using measures of aerosol bolus dispersion for possible clinical applications.

Aerosol Bolus Dispersion and Recovery in a Human and Dog Airway Cast

In recent years methods in lung diagnostics have been developed using the aerosolbolus inhalation technique (Heyde etr al., 1988; Anderso n et al., 1989 Schul; z et al.,1995; Blanchard 1996). A bolus is a small volume of aerosol sandwiched inparticle-free air and inhaled into different volumetric regions of the lung. Duringinhalation and exhalation the original small bolus is dispersed over a larger volume.This dispersion is caused by convective mixing in the airways and by intrinsicparticle motion. Because particles in the size range between 0.2 and about 1 umhave low intrinsic motion, they can be used as tracers of the convective air transportin the lungs. The extent of broadening of the bolus measured in the exhaled air is ameasure of the convective mixing during inhalation and exhalation, Blanchard(1996).The bolus inhalation technique can also be used to deliver aerosol into specificvolumetric regions of the lungs. If a bolus is inhaled near the end of an inhalation,the aerosol particles cannot penetrate deep into the lungs and should be deliveredpreferentially to the tracheobronchial airways. In order to determine where theparticles from an inhaled bolus are located within the lungs at end inhalation,dispersion and recovery studies were made in a dog and a human airway cast.

Aerosol bolus dispersion and aerosol-derived airway morphometry: assessment of lung pathology and response to therapy, Part 1.

review discusses the potential utility of two methods using inhaled aerosols to detect and diagnose lung disease and to evaluate the efficacy of therapy. Aerosol bolus dispersion measures convective gas mixing; aerosol-derived airway morphometry assesses the calibers of airway and airspaces. These two methods are discussed in terms of their ease of use (simplicity and acceptability) and current data regarding their validity, reproducibility, specificity, sensitivity, and detection of lung improvement with therapy. Part 1 of this review focuses upon aerosol bolus dispersion; Part 2(1) focuses upon aerosol-derived airway morphometry. Aerosol bolus dispersion has many features that make it clinically attractive. It is simple to administer and patients can successfully perform the maneuvers. It detects known alterations in the lungs. It is reproducible and has high specificity and sensitivity. However, every lung disease or condition known to be detected by aerosol bolus dispersion is also detected by spirometery, maximal expiratory flow-volume curves, or another conventional lung function test. This, aerosol bolus dispersion appears best reserved as a specialized method to supplement conventional lung function tests and to characterize convective gas transport.

Aerosol Bolus Dispersion and Aerosol-Derived Airway Morphometry: Assessment of Lung Pathology and Response to Therapy, Part 2

ABSTRACT This review discusses the potential utility of two methods using inhaled aerosol to detect and diagnose lung disease. Part 1, published earlier,(1) focused upon aerosol bolus dispersion, which measures convective gas mixing. Here, Part 2 focuses upon aerosol-derived airway morphometry (ADAM), which assesses the diameters of airways and acini. This method is discussed in terms of its validity, ability to detect known interventions and diseases, and reproducibility (administering and performing this procedure were already discussed(1). With ADAM, airway and acinar diameters are expressed in terms of the effective airway diameter (EAD), which can be measured as a function of volumetric depth in the lungs. Evidence that ADAM is valid is provided by studies showing EAD agrees well with morphometric indices of airway and acinar size, especially once the distribution of aerosol is accounted for, and changes appropriately in response to known interventions and several diseases. Of particular note is the ...

Dispersion of aerosol boluses in the human lung: dependence on lung volume, bolus volume, and gender

The dispersion of aerosol boluses in the human lungs has been studied in health and disease, usually as a means of investigating convective mixing. However, there are limited data on the roles of critical factors, such as the volume of inhaled boluses, lung inflation, and gender on dispersion. To examine these factors, we measured the difference in volume variance between exhaled and inhaled boluses (sigma 2V) of a 0.5-micron aerosol in 11 healthy male and 12 healthy female subjects as a function of tidal volume (VT = 1,000 and 1,500 ml in females and 1,000 and 2,000 ml in males), bolus penetration volume (Vi at 250-ml increments over each VT), and bolus volume (target VBol = 75, 150, and 300 ml). Analysis of variance showed marginally significant gender effects (P = 0.073) on sigma 2V, with sigma 2V greater in males than in females. There was also a significant effect of VBol on sigma 2V (P < 0.001). A Vi-dependent mean volume shift between inhaled and exhaled boluses (delta V) was observed at all Vi except 500 ml. The observation of gender and VBol effects and the existence of a nonzero delta V suggest that convective mixing mechanisms other than longitudinal dispersion alone occur in the healthy lung. The lack of VT dependence suggests a minimal role of lung inflation above functional residual capacity on dispersion. The dependence of sigma 2V on Vi2 up to 1,750 ml and minimal VBol effects demonstrates that convective mixing processes continue far into the gas exchange regions of the lung and support a significant role for axial streaming.

Dispersion of aerosol boluses in packed beds

Dispersion of aerosol boluses in packed beds

Aerosol bolus dispersion and effective airway diameters in mildly asthmatic children

The contribution of aerosol techniques, the estimation of aerosol bolus dispersion and effective airway dimensions, to the clinical diagnosis of paediatric asthma was studied. In 47 children, aged 11 +/- 2 yrs, with mild asthma (forced expiratory volume in one second (FEV1) 83 +/- 9% of forced vital capacity (FVC)) effective airway diameters were derived from the recovery of inhaled 1 micron sebacate droplets. Intrapulmonary dispersion of inhaled boluses of 0.4 micron droplets was studied, by characterizing the concentration distributions of droplets in the exhaled air by their standard deviation and skewness. Effective airway diameters increased in asthmatic subjects with increasing body size, and did not differ from those obtained in 16 healthy children of similar age and height. Standard deviation and skewness of particle boluses exhaled from shallow lung depths were higher in the asthmatic children than the healthy children (e.g. standard deviation 91 +/- 17 ml vs 79 +/- 15 ml, skewness 0.38 +/- 0.16 vs 0.23 +/- 0.16, respectively, for boluses in 140 ml lung depth). The sensitivity and specificity of bolus dispersion to detect alterations in lung function was comparable to that of FEV1/FVC, the most sensitive conventional lung function parameter in the present study. There was no correlation between body height or lung function and bolus parameters. We conclude that aerosol measurements do not provide an obvious benefit for the clinical diagnosis of mild paediatric asthma, but bolus dispersion supplies additional information on alterations in convective gas transport in the diseased lung.

The macrotransport of aerosol particles in the lung: Aerosol deposition phenomena

The macrotransport model of lung dispersion ( Edwards, 1994) is generalized to incorporate phenomena involving the nonconservation of gas and/or aerosol species in the airways and acini of the human lung during a single breath. The three principal parameters measured in single-breath gas or aerosol bolus dispersion experiments, namely, net deposition rate ( K ∗ ), mean bolus velocity ( U ∗ ) and effective dispersion coefficient ( D ∗ ), are theoretically determined in terms of the detailed microtransport, branch-level phenomena underlying them. Explicit formulas are provided for the macroscale coefficients ( K ∗, U ∗, D ∗ ). Additionally, a formula is provided for a coefficient A ∗ that serves to characterize a novel “apparent initial condition” to be imposed upon the aerosol concentration profile as viewed from its coarse-grained level. Numerical calculations are made in the case of aerosols. These are based upon a symmetrical Weibel model A geometry, and employ the deposition model of Landahl (1950) for assigning constitutive laws to the branch-level deposition-rate parameters that underly the theory. Branch-level dispersion coefficients are described by an axial-streaming constitutive law, as in the previous contribution, while taking explicit account of the diminution of axial streaming caused by aerosol deposition. Comparison is made with the aerosol bolus experimental data of Heyder et al. (1988) and Anderson et al. (1989) . Predictions of net aerosol deposition in the human lung as a function of aerosol particle size are compared with predictions made on the basis of former aerosol-deposition theories, as well as with additional aerosol-deposition data appearing in the literature. Very good agreement is found for all of these comparisons.

Dispersion of aerosol particles in an airway cast of a dog.

Aerosol bolus dispersion was measured in the first branching generations of a replicate hollow cast. The cast was made from a solid cast of a beagle-dog tracheobronchial tree. The dispersion was measured after penetration of boluses into different volumetric depths, with different particle sizes and flow rates into the cast. An enhanced flow rate led to a decreasing dispersion in the cast. Particle size up to about 4 microns has no significant effect on dispersion.

One-dimensional simulation of aerosol transport and deposition in the human lung

One-dimensional transport models (trumpet model and multibranch-point model) derived from those developed to study gas transport and mixing in the lung are used to simulate aerosol deposition as a function of particle diameter and aerosol dispersion of inhaled bolus in human lungs. In agreement with previous studies, aerosol deposition is satisfactorily simulated by the different models. However, the differences between simulations and experiments of aerosol bolus dispersion suggest that current models are not realistic. This is probably due to the intrinsic limitations of the one-dimensional models to describe aerosol transport in the lung periphery. We show that future model analyses can probably use a symmetric acinar structure like the classic Weibel model of the lung but that multidimensional particle transport equations are required. Furthermore, a rigorous description of aerosol dispersion in the oral-laryngeal path is also needed.

Detection of small airway dysfunction in asymptomatic smokers using aerosol bolus behavior.

Tests using inhaled particles assess ventilatory nonuniformities and may be sensitive to early changes in the small airways of cigarette smokers. We measured aerosol bolus behavior in 20 asymptomatic smokers and 20 age- and sex-matched nonsmokers for comparison with pulmonary function parameters including the single-breath nitrogen test. Narrow boluses containing 1-micron particles were introduced into 1-I breaths and inhaled to varying lung depths. We examined changes in bolus shape between inhalation and exhalation using plots of aerosol concentration versus respired volume for measurement of bolus dispersion, volumetric change in mean location (mean shift), and quantitative particle deposition. We found exhaled bolus dispersion to be significantly increased in smokers compared with nonsmokers. Volumetric mean shift was significantly different in smokers at shallow lung depths, with the center of bolus mass occurring later in exhalation. FEV1/FVC in smokers was significantly inversely correlated with dispersion at deeper lung depths and with mean shift at all lung depths. Smokers with abnormal spirometry (n = 4) or an abnormal single-breath nitrogen test (n = 7) had significantly increased dispersion compared with smokers with normal pulmonary function tests. We conclude that aerosol bolus dispersion is a useful tool for examination of small airway function in asymptomatic smokers.

Aerosol bolus dispersion in the respiratory tract of children.

To investigate mechanisms of intrapulmonary convective gas transport, aerosol bolus dispersion was measured in 16 healthy children aged 7-11 years. Subjects inhaled 50-mL aerosol boluses consisting of 0.4-micron droplets of di(2-ethylhexyl) sebacate suspended in air into volumetric lung depths between 95 and 540 mL. Bolus dispersion was quantified by volumetric bolus half-width and by volumetric standard deviation of particle concentrations. Bolus half-width increased from a mean of 160 mL to 360 mL with increasing lung depth, the regression being a power law with an average exponent of 0.48. Standard deviation increased from 68 to 136 mL with the 0.42th power of volumetric penetration. There was no correlation of bolus dispersion with age, body height, or lung function parameters, except for boluses penetrating very deep into the lung where dispersion was weakly related to lung volume. The results obtained in children did not differ from those found in an adult population in an earlier study. It was concluded that airway size per se does not have a strong influence on bolus dispersion. Rather, parameters of airway geometry may be among the dominating factors influencing the fate of inhaled particles.

Respiratory responses to repeated prolonged exposure to 0.12 ppm ozone.

Repeated exposure to high concentrations of ozone results first in augmentation (typically on the second day) and then attenuation of pulmonary response in humans. To determine the effects of repeated prolonged low-concentration ozone exposure, we exposed 17 healthy nonsmoking male subjects to 0.12 ppm ozone for 6.6 h on 5 consecutive days. Subjects were also exposed once to filtered air. Volunteers exercised at a ventilation of approximately 39 L/min for 50 min of each hour during the exposure. Spirometry, plethysmography, and symptom responses were obtained before, during, and after each exposure. Nasal lavage and aerosol bolus dispersion were obtained before and after exposure. Spirometry decreased and symptoms increased on the first day. Responses were less on the second day compared with those on the first day, and they were absent compared with control values on the subsequent 3 days of ozone exposure. Percent change in FEV1 after ozone exposure compared with that after air exposure averaged -12.79, -8.73, -2.54, -0.6, +0.18% for Days 1 to 5 of ozone exposure, respectively. FEV1 responses ranged from a zero to 34% decrease on Days 1 and 2. After each exposure, we determined the ratio of SRaw after inhaling a fixed dose of methacholine to SRaw after inhaling saline aerosol, as an index of airway responsiveness. Airway responsiveness was significantly increased after each ozone exposure. The mean ratios were 2.22, 3.67, 4.55, 3.99, 3.24, and 3.74 for filtered air and ozone Days 1 to 5, respectively. Symptoms of cough and pain on deep inspiration increased significantly on ozone Day 1 only.(ABSTRACT TRUNCATED AT 250 WORDS)

Accuracy and resolution power of aerosol-derived airway morphometry in a simple lung model.

Aerosol-derived airway morphometry (ADAM) uses sedimentational deposition of monodisperse aerosol particles during breathhold to estimate intrapulmonary air-space dimensions. To determine the accuracy and resolution power of this technique a simple physical lung model comprised of uniform glass beads was investigated. Using the chordlength model, aerosol recovery from this porous medium was calculated by computer simulation of the geometrical structure of air-spaces between glass beads. The results of this calculation were then compared with experimental data: Calculated and measured air-space dimensions differ less than 2% for particles with diameters above about 1 micron. The measured air-space dimension can be described geometrically by the mean chordlength of the porous medium. To estimate the resolution power of ADAM, a defined change in air-space dimensions represented by a horizontal air slit was introduced into the porous medium. This air slit induces a marked increase of measured air-space dimensions. The volumetric width of this increase is the higher the deeper the slit is situated within the medium. Intercomparison of these data with the results of aerosol bolus dispersion measurements suggests that the resolution power of ADAM is decreased by the same mechanisms that increase dispersion of aerosol boluses, demonstrating the close relationship between both methods.

The Effect of Convective Mixing on Particle Transport in the Human Respiratory Tract

Aerosol inhalation studies have demonstrated the significance of convective mixing for gas and particle transport in the lungs. Convective mixing can be determined experimentally by measuring as a function of volumetric depth the dispersion of an aerosol bolus while this bolus penetrates into a defined lung volume during inspiration and is recovered from this depth upon expiration. Since convective mixing may be influenced by the variability and asymmetry of the branching airway geometry, a recently developed model of aerosol transport in a random airway system has been applied to study aerosol bolus dispersion. The effect of convective mixing has been considered in effect by diffusivity. It modifies the penetration of individual particles into the lung, the time distribution of exhaled particles, and mixing in the alveolar region, finally resulting in the experimentally observed dispersion of a narrow inhaled aerosol bolus.

Aerosol bolus dispersion and convective mixing in human and dog lungs and physical models.

The dispersion of aerosol boluses in the lung is a probe for convective mixing and has been proposed as a marker for abnormal lung function. To better understand the factors underlying this phenomenon, aerosol dispersion was compared in human subjects, dogs, and various physical models. In all systems, dispersion increased with the volumetric penetration of the aerosol bolus. The rate of this increase was 83% greater in humans compared with dogs. Dispersion in dogs was close to that in a packed bed with beads of 2.5 mm. Aerosol dispersion decreased with increasing flow rate in human subjects. An artificial larynx inserted into the straight tube caused a 33% increase in dispersion. In humans, aerosol dispersion was significantly correlated with forced expired flow between 25 and 75% of vital capacity. A 2-s pause between inspiration and expiration increased dispersion 23-58% in three isolated dog lungs but did not affect dispersion in the packed bed. The data suggest that lung geometry, flow rate, particle mobility, and the larynx all significantly affect aerosol dispersion by influencing the reversibility of aerosol transport between inspiration and expiration.

Early Response of the Canine Respiratory Tract Following Long-Term Exposure to a Sulfur(IV) Aerosol at Low Concentration. IV. Respiratory Lung Function

Respiratory function was studied in eight beagle dogs at the end of a 290-day exposure to a sulfur(IV) aerosol [0.3 mg m−3 S(IV)]and compared to lung function parameters in three dogs exposed to clean air during the same period. The lung mechanics were characterized by lung volumes and quasistatic and dynamic compliances of lungs and thorax. Gas exchange and gas transport were estimated by carbon monoxide rebreathing, single-breath and multiple-breath inert gas washout, and the study of aerosol bolus dispersion. We found a significant decrease in specific lung compliance (728 ± 8 vs. 149 ± 9 ml hPa−1 p<.05) and a tendency toward a fall in membrane diffusing capacity (21.5 ± 2.7 vs. 25.7 ± 4.3 ml min−1 hPa −1) in S(IV)-exposed dogs. The change in membrane diffusing capacity correlated with a decrease in alveolar surface area as demonstrated by postmortem morphometric analysis flakenaka et al., 1992). No differences were observed between exposed dogs and controls in any of the other parameters of lung function. The results show that chronic inhalation of low levels of S(IV) aerosol induces minor changes in respiratory function.

Dispersion of aerosol boluses in the human tracheo-bronchial-tract during periods of breathholding

To study the behaviour of inspired aerosols in human conducting airways during breathholding, inhalation experiments were carried out using monodisperse areosols with an aerodynamic particle diameter of about 1 μm. With a newly developed aerosol inhalation device (Scheuch et al. 1989) very small volumes of aerosols (boluses) were injected in a 1000 cm 3 clean air inspiration and after a breathholding period (t b) dispersion of these boluses were measured in the exhaled air with a laser photometer. The boluses were inhaled to volumetric lung depths (V L) between 25 and 250 cm 3 and breathholding periods (t b) were chosen up to 60 s. Injecting the boluses to V L > 50 cm 3 bolus dispersion increased with increasing t b up to a maximum and decreased with even longer t b. This behaviour is mainly caused by cardiogenic flow oscillations (increase of broadening) and deposition due to gravitational settling (decrease).

Mechanical factors in distribution of pulmonary ventilation.

Mechanical factors in distribution of pulmonary ventilation.