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Biomedical subjects

W Stahlhofen

Publications and source records attributed to W Stahlhofen.

At least 19 recordsLinked to original sources
PubMed1999

A new methodology for controlled particle inhalation by small rodents.

In order to investigate the deposition, retention, and clearance mechanisms implicated in particle inhalation under standardized conditions, we developed a continuous negative-pressure ventilation system, whereby the breathing pattern in small rodents could be controlled during exposure to aerosols. Using an on-line open-flow set-up, 19 anesthetized, intubated, and paralyzed Syrian golden hamsters, individually contained within a whole-body box, were artificially ventilated under the said continuous negative-pressure conditions, 1 of 5 different combinations of breathing frequency and tidal volume being established. The animals were then exposed to aerosols containing 6-micron diameter polystyrene spheres, and the deposition of particles in the conducting airways was monitored photometrically. During exposure, the level of respiration (mean lung inflation) was stabilized by means of a negative-pressure vent. Breathing frequency and tidal volume, as well as the compliance of the system, remained virtually unchanged during the course of a single experiment, and in each case, a reproducible deposition of particles was achieved. Our findings indicate that tidal volume, but not breathing frequency, has a marked influence on the particle deposition ratio. Breathing frequency exerts opposing and counterbalancing effects on this latter parameter by enhancing the impaction of particles on the one hand, and by decreasing sedimentation on the other.

Administration, Inhalation↗
PubMed1999

Regional deposition and retention of particles in shallow, inhaled boluses: effect of lung volume.

The regional deposition of particles in boluses delivered to shallow lung depths and their subsequent retention in the airways may depend on the lung volume at which the boluses are delivered. To evaluate the effect of end-inspiratory lung volume on aerosol bolus delivery, we had healthy subjects inhale radiolabeled, monodisperse aerosol (99mTc-iron oxide, 3.5-microm mass median aerodynamic diameter) boluses (40 ml) to a volumetric front depth of 70 ml into the lung at lung volumes of 50, 70, and 85% of total lung capacity (TLC) end inhalation. By gamma camera analysis, we found significantly greater deposition in the left (L) vs. right (R) lungs at the 70 and 85% TLC end inhalation; ratio of deposition in L to R lung, normalized to L-to-R ratio of lung volume (mean L/R), was 1.60 +/- 0.45 (SD) and 1. 96 +/- 0.72, respectively (P < 0.001 for comparison to 1.0) for posterior images. However, at 50% TLC, L/R was 1.23 +/- 0.37, not significantly different from 1.0. These data suggest that the L and R lungs may be expanding nonuniformly at higher lung volumes. On the other hand, subsequent retention of deposited particles at 2 and 24 h postdeposition was independent of L/R at the various lung volumes. Thus asymmetric bolus ventilation for these very shallow boluses does not lead to significant increases in peripheral alveolar deposition. These data may prove useful for 1) designing aerosol delivery techniques to target bronchial airways and 2) understanding airway retention of inhaled particles.

Adult↗
PubMed1998

Bronchial airway deposition and retention of particles in inhaled boluses: effect of anatomic dead space.

The fractional deposition of particles in boluses delivered to shallow lung depths and their subsequent retention in the airways may depend on the relative volume and size of an individual's airways. To evaluate the effect of variable anatomic dead space (ADS) on aerosol bolus delivery we had healthy subjects inhale radiolabeled, monodisperse aerosol (99mTc-iron oxide, 3.5 micron mean mondispersed aerosol diameter) boluses (40 ml) to a volumetric front depth of 70 ml into the lung at a lung volume of 70% total lung capacity end inhalation. By using filter techniques, aerosol photometry, and gamma camera analysis, we estimated the fraction of the inhaled boluses deposited in intrathoracic airways (IDF). ADS by single-breath N2 washout was also measured from 70% total lung capacity. Results showed that among all subjects IDF was variable (range = 0.04-0.43, coefficient of variation = 0.54) and increased with decreasing ADS (r = -0.76, P = 0.001, n = 16). We found significantly greater deposition in the left (L) vs. right (R) lungs; mean L/R (ratio of deposition in L lung to R lung, normalized to ratio of L-to-R lung volume) was 1.58 +/- 0.42 (SD; P < 0.001 for comparison with 1.0). Retention of deposited particles at 2 h was independent of ADS or IDF. There was significant retention of particles at 24 h postdeposition (0.27 +/- 0.05) and slow clearance of these particles continued through 48 h postdeposition. Finally, analysis of central-to-peripheral ratios of initial deposition and 24-h-retention gamma-camera images suggest significant retention of insoluble particles in large bronchial airways at 24 h postdeposition (i.e., 24 h central-to-peripheral ratio = 1.40 +/- 0. 44 and 1.82 +/- 0.54 in the R and L lung, respectively; P < 0.02 for comparison with 1.0). These data may prove useful for 1) designing aerosol delivery techniques to target bronchial airways and 2) understanding airway retention of inhaled particles.

Adult↗
PubMed1997

Probing mechanical properties of living cells by magnetopneumography.

Magnetopneumography (MPG) has been used to study long-term particle clearance from human lungs as well as cellular motility of pulmonary macrophages (PMs). This study describes an extension of the method enabling the measurement of mechanical properties of PM cells in vivo. Ferromagnetic microparticles are inhaled and then retained in the alveolar region of the lungs, where they are phagocytized within hours by PMs. The magnetic particles can be rotated in weak magnetic fields, and the response to this twisting shear (force) is detected as a macroscopic magnetic field producing a measure of cytoskeletal mechanics. Cytoplasmic viscosity is very high compared with that of water and is strongly non-Newtonian. Under rotational stresses from 0.4 to 6.4 Pa, it acts like a pseudoplastic fluid showing a characteristic shear rate dependence. The viscosity as well as the stiffness of the cytoskeleton increases with increasing shear stress as seems typical for living tissue and evidence for an intact cytoskeletal matrix. The particle recoil as measured by the amount of recoverable strain following a short twisting force describes a cytoplasmic elasticity that depends on both level and duration of stress. These investigations on the mechanical properties of living human cells are promising and should lead to better understanding of cellular dysfunction in disease as well as pathways for drug administration.

Adult↗
PubMed1996

Smoking impairs alveolar macrophage activation after inert dust exposure.

Magnetopneumography was applied to investigate intracellular phagosome motion in alveolar macrophage cells of healthy subjects (non-smokers and smokers). Ingested magnetic microparticles are inhaled and phagocytized by alveolar macrophages within hours. Thereby the particles are transferred into phagolysosomes. After magnetization the particles produce a macroscopic magnetic field of the lungs. Cellular motility causes a decay of the field (relaxation) by stochastic disorientation of the dipole particles (phagolysosomes) in the cells. Our studies have shown that the deposition of magnetite test particles induces a non-specific activation of the macrophage cells with a faster relaxation. This activation vanishes within the first day after particle deposition. This macrophage activation due to dust exposure was not present in smokers. It follows that cigarette smoking either causes a damage of the cellular defense or causes an adaptation of the macrophage cells to the permanent cigarette smoke inhalation.

Administration, Inhalation↗
PubMed1996

Thirty month variability of aerosol pulse dispersion and conventional lung function parameters in healthy middle aged smokers and nonsmokers.

Chronic cigarette consumption is a generally accepted reason for the development of chronic obstructive pulmonary disease (COPD). COPD correlates to histomorphological parameters of lung structure as well as pulmonary function tests (PFT). COPD related changes affect PFT determined by conventional methods (bodyplethysmography, spirometry) as well as parameters of convective gas mixing. This study evaluates the diagnostic potential of a non-invasive aerosol method for the discrimination between healthy smokers and nonsmokers in comparison to conventional PFT. The aerosol method is based on the inhalation of small aerosol pulses suspended in particle free air and determines their changes during the breathing maneuver. Changes of aerosol pulse parameters (APP) are used to describe the convective component of gas mixing during ventilation. PFT and APP were determined in 40 healthy subjects (nonsmoker: 51.1 +/- 1.5 years; smoker: 49.6 +/- 1.5 years, 39.1 +/- 2.2 pack years) before and after a time interval of 30 months. Conventional PFT in smokers and nonsmokers showed no relevant differences between the values at the beginning and the end of the observation period. Thirty months later, at the end of the observation interval, a very similar behavior of the APP was obtained, which strongly confirmed the prior observed differences between smokers and nonsmokers. The data suggest that cigarette smoke-induced variations of lung function are also detectable in clinically asymptomatic smokers. Even in cases of normal PFT, most APP are able to discriminate between healthy smokers and nonsmokers. Since PFT showed only minor differences between both groups, it is indicated that APP are superior to PFT in the detection of early disturbances of lung ventilation in healthy smokers. Mean values of PFT and APP in smokers and nonsmokers showed a high reproducibility of the data obtained at the beginning of the study as well as at the end of the observation period. The data of our study further confirm that parameters of pulmonary gas exchange and gas mixing are affected by cigarette smoke at an earlier time than parameters of breathing mechanics.

Aerosols↗
PubMed1996

An approach to deposition and clearance measurements in human airways.

By using the aerosol bolus inhalation technique, aerosol particles can be delivered into the airways of the human respiratory tract. For that purpose the aerosol bolus is injected near the end of a clean air inhalation. It could be shown experimentally and theoretically that the particles were only deposited in the airways. Radioactive labeled particles were deposited with this technique and clearance from the airways was determined. It could be shown that the mucociliary clearance from the airways was particle size dependent. The clearance efficiency from the airways increased with increasing particle size.

Administration, Inhalation↗
PubMed1994

In vivo and in vitro studies of the cellular defense system of the human lung.

Magnetic microparticles were used to investigate the defence system of the human lungs against foreign material. About 0.5 mg of spherical monodisperse magnetite particles were deposited in the alveolar region of the human lung by voluntary inhalation. After primary magnetization a remanent magnetic field (RMF) of the lung can be measured that allows estimation of the amount of dust retained in the lung. The decay of this RMF, called relaxation, results from a misalignment of the dipole particles due to the activity of pulmonary macrophages. This macrophage activity was characterized by a cell energy Ez. With a secondary magnetization the lung can be remagnetized by rotation of the dipole particles. This allows estimation of the intracellular viscosity and the motility of the alveolar macrophages in vivo. The macrophage cell-line J774 was used to verify the dynamic processes of the magnetic particles within the cells in vitro. In vitro and in vivo relaxation curves of polydisperse and of spherical monodisperse magnetite particles are presented. Thermal relaxation of mono-disperse and polydisperse particles within a viscous standard could be verified with the Brownian rotary diffusion model. Relaxation with monodisperse particles was double exponential in vivo as well as in vitro, suggesting that 2 different viscous compartments of the cytoplasm should be considered. Relaxation in the macrophage cell-line J774 was particle-size-dependent.

Administration, Inhalation↗
PubMed1994

[Granulometry and measurement of a aerosol drug deposit (fusafungine) in normal and pathological airways].

We measured with a laser velocimeter granulometric deposit of an aerosol anti-infectious agent, fusafungin, administered with a controlled inhalator. Total drug deposit was determined on the basis of a granulometric spectrum of the polydispered aerosol (mass mean aerodynamic diameter (MMAD) = 2.8 +/- 1.7 microns) and dispersion in the airways was estimated using the Stahlhofen model. We first compared deposits obtained with oral inhalation in 19 normal subjects and 20 patients with chronic obstructive lung disease. Total deposit in the airways of patients with chronic obstructive lung disease (82%) was not significantly different from that in normal subjects (85%). Estimated dispersion in normal airways was 27% in the alveoles, 8.4% in the tracheobronchic region and 23.5% in the extrathoracic regions. We then compared deposits after nasal inhalation in 22 normal subjects and 21 patients with rhinitis: nasal deposit was significantly greater in patients with rhinitis (54.5%) than in controls (44.7%). We conclude that such an inhalator can be adapted for local treatment of ENT infections and upper respiratory infections. Deposit is not modified in case of obstructive bronchopathy.

Adult↗
PubMed1994

[Long-term effect of the beta 2-sympathomimetic formoterol in young smokers--study of duration and site of effect of bronchodilatation using conventional methods of lung function and monodispersed aerosols].

Formoterol is a novel selective beta 2-sympathomimetic inducing bronchodilatation after inhalation or oral application. Compared to other beta 2-sympathicomimetics the substance begins to act very rapidly even at a much lower dosage level, while it remains effective for at least 12 hours. In the present study the bronchodilatory effect of 24 micrograms MDI formoterol was investigated in 18 healthy smokers between 20 and 30 years of age means. Measurement was effected by means of conventional lung function diagnostics (body plethysmography, spirometry) and an biophysical aerosol measurement method for determining the effective airways dimensions (EAD). This method is based on the gravitational losses of a previously inspired monodisperse model aerosol during apnoea periods of different duration. It enables determination of the EAD as a function of the volumetric lung depth (VLT). A marked and universally measurable bronchodilatation is detectable directly after formoterol has been inhaled. The longterm action of formoterol was confirmed for more than 15 hours after application, using the conventional lung function test and the EAD method. Over and above this the EAD determination showed that the bronchodilatory effect was much more marked in the central airways than in the periphery of the lungs, thus confirming the effect generally described for beta 2-sympathomimetics as being mainly directed towards the central airways region.

Administration, Inhalation↗
PubMed1993

Behaviour of magnetic micro-particles in the human lung.

Magnetic micro-particles were used to investigate the defence system of the human lungs against foreign material. After primary magnetisation a remanent magnetic field (RMF) of the lung can be measured that allows estimation of the amount of dust retained in the lung. After calibration of the system with a lung phantom the magnetic contamination retained in the lungs of dental technicians and welders was estimated at mean values of 22 and 500 mg respectively. In normal controls only 0.3 mg was found. About 0.5 mg of spherical monodisperse magnetite particles was deposited in the alveolar region of the lung by voluntary inhalation. The decay of the RMF, called relaxation, results from a misalignment of the dipole particles due to the activity of pulmonary macrophages. This macrophage activity is characterised by a cellular energy Ez. With a secondary magnetisation the lung can be remagnetised by rotation of the dipole particles. This allows an estimation of the intracellular viscoelasticity and the motility of the alveolar macrophages in vivo. Secondary magnetisation and relaxation curves of spherical monodisperse magnetic particles are presented. Intracellular viscosity was estimated to be n approximately equal to 100 Pa.s at shear rates near 0.01 s-1, the rigidity modulus being v approximately equal to 4-8 Pa. Macrophage activity was described by a cellular energy EZ approximately 5 x 10(-18) J. Additionally, non-magnetic aerosol exposure resulted in a faster relaxation, which was interpreted to be due to activation of the macrophages. The magnetite particles were cleared with a half-time of approximately 110 days.

Administration, Inhalation↗
PubMed1992

Investigation of the defense system of the human lungs with ferrimagnetic particles.

Magnetic microparticles were used to investigate the defense system of the human lungs against foreign material. About 0.5 mg of spherical monodisperse magnetite particles were deposited in the alveolar region of the human lung by voluntary inhalation. After primary magnetization a remanent magnetic field (rmf) of the lung can be measured that allows estimation of the amount of dust retained in the lung. The decay of this rmf, called relaxation, results from a misalignment of the dipole particles due to the activity of pulmonary macrophages. This macrophage activity was characterized by a cell energy E z. With a secondary magnetization the lung can be remagnetized by rotation of the dipole particles. This allows estimation of the intracellular viscosity and motility of the alveolar macrophages in vivo. Secondary magnetization and relaxation curves of spherical monodisperse magnetite particles are presented. Intracelluar viscosity was estimated to be n approximately equal to 100 Paxs by a shear-rate near 0.01 s -1, macrophage activity was E z approximately equal to 5x10 -18 J. Aerosol exposure resulted in a faster relaxation, which was interpreted to be due to activation of the macrophages. The magnetite particles were cleared with a half-time of approximately equal to 110 days.

Humans↗
PubMed1990

[Measuring human mucociliary clearance].

Using a new inhalation technique, it is possible to inject aerosol boluses of defined volume at any moment during inspiration into the inhaled air. Deposition of particles in different lung depths was achieved by holding the breath at end-inspiration. Particle clearance of the inhaled radioactively labelled particles was determined by measuring the radioactivity retained in the lungs as a function of time after inhalation. Even for shallow volumetric lung depths as small as 35 cm3 slow clearance of a significant fraction of the deposit has been observed.

Aerosols↗
PubMed1981

Biological variability of regional deposition of aerosol particles in the human respiratory tract.

Regional deposition of inhaled particles was studied experimentally for 9 health subjects breathing the same aerosol under the same breathing conditions in order to evaluate intersubject variability of regional deposition. A great intersubject variability of extrathoracic, tracheobronchial and alveolar deposition was found. The highest one was observed for particle deposition in the extrathoracic airways. This biological variability of regional deposition has to be taken into account for considerations of health related aspects of aerosol inhalation.

Aerosols↗
PubMed1981

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↗
PubMed1981

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↗