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J Heyder

Publications and source records attributed to J Heyder.

90 records · Page 5Linked to original sources

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.

Aerosols↗

Intercomparison of regional deposition of aerosol particles in the human respiratory tract and their long-term elimination.

Human chest clearance of Teflon particles with an aerodynamic diameter of 4.7 micrometers tagged with 198Au or 111In was studied with two apparatuses and two gamma-ray spectrometers for the external detection of the activity deposited in the respiratory tract. Approximately the same chest retention function was measured with two gamma-ray spectrometers when the subjects inhaled equal aerosols under equal breathing conditions. The long-term clearance rate following the short-term elimination of particles from ciliated airways was slower for Teflon particles (mean half-time 105 days for 111In-labeled particles and 128 days for 198Au-labeled particles) than for iron oxide particles of the same size (mean half-time about 60 days). It is suggested that insoluble particles of this size studied are cleared with a half-time of about 120 days within the first 2 weeks after completion of mucociliary clearance. Regional deposition did not differ between the iron oxide and Teflon particles.

Adult↗

Experimental determination of the regional deposition of aerosol particles in the human respiratory tract.

The experimental techniques and the results of inhalation studies with radioaerosols on normal non-smokers for mouth-breathing are described and discussed. Monodisperse iron oxide particles tagged with 198Au are produced with a spinning top generator in the aerodynamic size range between 1 to 10 micrometers. An aerosol inhalation apparatus enables the subjects to breathe under standardized conditions with respect to tidal volume and breathing frequency. The calculation of total deposition is based upon measurements of the number of in- and exhaled particles per breath by means of photometric methods and pneumotachography. The retention of the radioactive particles present in the body after aerosol administration is measured with a body counter designed and constructed for these experiments. Retention measurements as functions of time after inhalation are carried out in extrathoracic-, chest- and stomach-position. The body counter consists of four shielded NaF(TI)-detectors. The geometrical arrangement, the collimation and the shielding of the four detectors have been optimized by computer calculations in such a way that the response of the counter is independent of the distribution of activity within the chest. Another characteristic feature of the body counter is its low sensitivity to neighboring organs and to neighboring regions within the respiratory tract. For the evaluation of extrathoracic deposition, the activity measured in the stomach immediately after inhalation is added to extrathoracic activity. The elimination of material from the chest (intrathoracic airways) is found to be much slower for the material deposited in the alveolar region (non-ciliated air spaces) than for the amount deposited in the tracheobronchial tree (ciliated airways). This allows the intrathoracic deposition to be divided into tracheobronchial and alveolar deposition by means of the different slopes of the normalized chest retention function. Different normalized chest retention functions are presented and analysed with respect to their different elimination rates belonging to the tracheobronchial and alveolar region. Total, tracheobronchial, alveolar and extrathoracic deposition data are reported in the aerodynamic diameter range between 1 and 10 micrometers.

Aerosols↗

Aerosol transport in the human lung from analysis of single breaths.

Experimental and theoretical results are presented for the single-breath inhalation of an aerosol with 0.5- and 1-micrometer particles of bis(2-ethylhexyl) sebacate droplets. Experimental results show that the recovery from the tidal volume decreases with increasing tidal volume and increases with increasing flow rate. The reserve volume recovery does not vary much with either flow rate or tidal volume. Experimental values for reserve volume recoveries for 1-micrometer particles were slightly larger than those for 0.5-micrometer particles, indicating intrinsic particle motion plays some role in the mixing process for larger particles. Calculated results from a convection-diffusion equation for the aerosol concentration are compared with the experimental results, with the aim of testing the hypotheses of the theoretical model. Detailed comparisons between theory and experiment for the exhalation profiles demonstrate that most of the mixing between the tidal and reserve volumes occurs in the alveolar region of the lung, as postulated in the model. Mechanical mixing in the upper airways plays a relatively minor role in the overall mixing process. Theoretical results for the recoveries show the same trends with tidal volume and flow rate as does experiment, and the agreement is good. Calculated values for the mixing of the tidal aerosol range from about 0.06 at a tidal volume of 400 cm3 to 0.23 at 2,000 cm3, and no variations with flow rate was found.

Aerosols↗

Deposition of aerosol particles in the human nose.

About 2000 breathing experiments were performed, involving four breathing manoeuvres, four volunteers, a wide range of particle diameters and various breathing patterns. Monodisperse droplets of bis(2-ethylhexyl) sebacate served as aerosol particles. The deposition of particles in the nose was calculated from total deposition of particles in the whole respiratory tract for mouth, nose, mouth-nose and nose-mouth breathing. This method allowed the determination of nasal deposition and nasal efficiency for inspiration and expiration. Total deposition was determined from measurements of the particle concentration and the respiratory volume flow rate. Considerable scatter of nasal deposition in the four subjects was found. At a constant tidal volume it rose rapidly with increasing flow rate. The nasal efficiences were found to be independent of tidal volume. For inspiration as well as expiration the nasal passages removed particles very efficiently by inertial impaction. However, inspiratory and expiratory nasal efficiences were different. The scatter of individual inspiratory efficiency could be considerably reduced by employing a mathematical relationship to describe inspiratory nasal efficiency which makes use of the pressure difference across the nose and nasopharynx during nose breathing.

Aerosols↗

Human alveolar long-term clearance of ferromagnetic iron oxide microparticles in healthy and diseased subjects.

Monodisperse ferrimagnetic microparticles (Fe3O4) with 1.3 microm geometric diameter were inhaled to study alveolar long-term clearance in healthy and diseased human subjects. Nineteen younger (age 20 to 39 years) and 20 older (age 40 to 65 years) healthy volunteers participated in the study as well as 15 patients with sarcoidosis (SAR), 12 patients with idiopathic pulmonary fibrosis (IPF), and 15 patients with chronic obstructive bronchitis (COB). In each group the subjects were divided into never smokers (NS) and active smokers (S). Clearance was measured by magnetopneumography (MPG) for 300 days after inhalation. In COB, 50% of the deposited particles were removed from the lungs after 2 days, indicating high bronchial deposits due to bronchial obstructions. In healthy NS, only 10% of the particles were removed after 2 days and cigarette smoking enhanced the fraction of fast-cleared particles. In subjects who smoked, slow clearance was significantly impaired (P < . 02). Clearance half-lives (in days) for younger, healthy, NS were 124 +/- 66 (mean +/- SD) compared to 220 +/- 74 for S. Similarly for older subjects, the timeswere 162 +/- 120 for NS and 459 +/- 334 for S. The impairment of alveolar clearance due to cigarette smoking increases by 5.7 +/- 1.3 days/pack-year (P < .01). Alveolar clearance was impaired in SAR and in IPF; half-lives were 275 +/- 109 days (P < .05) and 756 +/- 345 days (P < .02), respectively, compared to healthy NS. Most COB patients were ex-smokers, their long-term clearance was 240 +/- 74 days, which is more than healthy NS (P < .01), but less than healthy S and might indicate a recovery of alveolar clearance. In view of studies using totally inert particles like Teflon, we conclude that the lung clearance measured with iron oxide tracer particles primarily reflects clearance by intraphagosomal particle dissolution within alveolar macrophages, which is impaired by cigarette smoke consumption and in patients.

Administration, Inhalation↗

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.

Aerosols↗

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.

Aerosols↗

Influence of gas composition on convective and diffusive intrapulmonary gas transport.

The influence of gas composition on convective and diffusive gas transport in the lungs was assessed by studying the dispersion of combined particle and argon (Ar) boluses induced by the passage through the lungs filled with three different gas mixtures. Particles, as a "nondiffusing gas," served as a tracer for convective gas transport, while the significance of diffusive gas transport was inferred from the difference in the behavior of Ar and particles. The lungs of six anesthetized and mechanically ventilated beagle dogs were equilibrated with air or either of the test atmospheres, He-O2 or SF6-O2, where nitrogen was replaced by helium (He) or sulfur hexafluoride (SF6). Due to differences in gas density and gas viscosity Reynolds numbers varied by a factor of twelve and Ar diffusivity by a factor of four between He-O2 and SF6-O2, suggesting that both kinds of intrapulmonary gas transport, convection and diffusion, should be affected. Combined particle and Ar boluses were inhaled into various lung depths and the extent of gas transport was inferred from changes in bolus shape induced by the passage through the lungs. In air, convective bulk gas transport generally followed the symmetric first-in, last-out principle and acted at all tested lung depths. Within the conducting airways, gas transport to the lung periphery was primarily due to convection but beyond these airways diffusion became rapidly significant. Breathing test atmospheres affects intrapulmonary gas transport only slightly. The extent of convective mixing was increased by 4% in SF6-O2 (p < .01) and reduced by 5% in He-O2 (p < .01) as compared to air. The symmetry of convective lung filling and emptying was slightly disturbed. In SF6-O2 the mean of the exhaled bolus was shifted by 8% toward the lung periphery. In He-O2 it was shifted by 4% toward the airway opening. In both test atmospheres exhaled Ar boluses were similar, suggesting that diffusive gas transport overwhelms the small changes in convective gas transport. Hence, factors other than gas composition-related flow characteristics, e.g., nonreversibility of in- and expiratory flow profiles or features of lung geometry, are the major determinants of gas transport in the lungs.

Animals↗

Influence of intrinsic particle properties on the assessment of convective gas transport by aerosol bolus technique.

Aerosol bolus measurements are increasingly being used in patients and healthy subjects to assess convective gas transport and mixing in the lungs. To investigate the extent to which intrinsic particle properties confound parameters derived for the assessment of intrapulmonary transport, bolus inhalation experiments were performed in six anesthetized, intubated, and mechanically ventilated beagle dogs using DEHS particles of 0.5, 1, or 2 microns diameter. Therefore, particle displacement by diffusion varied by a factor of two, settling velocity by a factor of 13, and particle inertia as inferred from the stopping distance by a factor of 16. By using a standardized breathing maneuver 6-mL boluses were inhaled into lung depths between 75 and 475 mL. Mode, half-width, and intrapulmonary particle deposition along with mean, standard deviation, and skewness of the particle concentration distributions in the expired air were determined. For all particle sizes studied particle deposition increased with increasing lung depth not exceeding 25% for 0.5-micron particles, but being 80% in deep lung regions for 2-micron particles. Whereas half-width and standard deviation exhibited only small differences between particle sizes (less than 20%), mode and mean of the exhaled bolus were clearly dependent on particle size, in particular for particles inhaled deep into the lung. No significant effects were detectable for the skewness. Hence, convective mixing assessed by half-width or standard deviation is only slightly dependent on particle size, but the estimate of convective bulk transport as inferred from the mean volume from which the bolus is exhaled is highly dependent on particle size. Yet, the intrinsic mobility of unit-density 0.5-micron particles was found to be small enough to consider these particles as ideal tracers for probing convective gas transport in the lungs.

Administration, Inhalation↗

Deposition pattern of droplets from medical nebulizers in the human respiratory tract.

Total and regional deposition data for aerosol particles in the human respiratory tract measured in normal mouth-breathing subjects are applied to aerosols from medical nebulizers. From deposition data as a function of particle size and respiratory parameters and from the droplet size distributions of various jet and ultrasonic nebulizers, integral mass depositions as a fraction of the aerosol entering the mouthpiece are determined for the total respiratory tract, the extrathoracic airways, the tracheobronchial tree and the alveolar region. Since the aim of inhalation therapy is the deposition of particles in that part of the respiratory tract which is to be treated, the results of this study may also be useful in finding out optimum conditions in cases of therapeutic applications.

Aerosols↗