[Pulmonary diagnosis with model aerosols. II: Aerosol bolus dispersion--a marker for convection gas transport. Basic principles and initial clinical results].
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Adult↗
Biomedical subjects
J Heyder
Publications and source records attributed to J Heyder.
[Diagnostic pneumology using model aerosols].
Clearance of Aerosol Particles from the Airways: Measurement of the efficiency and kinetics of particle clearance from the airways is dependent on the site of particle deposition within the lungs. Insoluble particles deposited in the alveolar region are mainly cleared by macrophages over a period of hundreds of days, whereas particles from the tracheobronchial airways are mainly cleared within hours or days by mucociliary clearance. We introduce a method for mucociliary clearance measurements called 'Radio-Bolus-Scintigraphy'. A small volume of radiolabelled aerosol particles sandwiched in clean air (aerosol bolus) is inhaled near the end of a tidal breath which leads to a preferential deposition of the particles in the airways. Particles were Fe3O4 labelled with 99mTc with an aerodynamic particle diameter of 3.5 microns (monodisperse). The retention of the particles within the lungs was detected by Gamma Camera and Human Scintillation Counter. 26 healthy subjects volunteered in this study (14 nonsmokers and 12 smokers). The half width of the mucociliary clearance was found to be 2.4 h in nonsmokers and 3.3 h in smokers (p < 0.05). Intersubject variability was small, 24 hours after inhalation 55% (+/- 6%) of the inhaled particles were still found in the airways of the subjects. No difference was found between nonsmokers and smokers. Good intersubject reproducibility makes this method useful in therapy control as well as in early diagnosis of changes in mucociliary clearance kinetics and efficiency.
Aerosols↗
[Depressed mood in the acute phase of first ischemic cerebral infarct].
In the acute phase of cerebral ischemia, 55% of the patients showed signs of mild depression after a period of 5-9 days. The development and intensity of depressive symptoms correlated strongly with the grade of functional impairment. A statistically less significant relationship was established between the depressive symptoms and low social status, higher age, lower predisease intelligence and accompanying symptoms of anxiety. Independent of antidepressive therapy, after 4 weeks an improvement in the initially registered functional and intellectual impairment as well as the depressive symptoms (prevalence rate 23.3%) was recorded. None of these parameters correlated with each other in any way. In conclusion, we interpreted these depressive symptoms as the result of reactive coping strategies during the acute phase of cerebral ischemia. In contrast to this, the aspect of gender showed no significant relationship to the resulting depressive symptoms. Furthermore, lesion location, lesion volume, and cortical atrophy and cognitive impairment proved to have no influence on depressive symptoms. This suggests that primary organic factors are not the cause of depression in connection with the acute stroke period.
Activities of Daily Living↗
The respiratory bronchiole of beagle dogs: structural characteristics.
The centriacinar regions are a central site of lung diseases and they are also considered to be susceptible to air pollutants. Dogs as well as humans and monkeys possess several generations of respiratory bronchioles. Commonly used small laboratory animals, however, have either no, or at most, a single short generation. Therefore, it is assumed that the response to air pollutants differs among animal species according to the presence or absence of the respiratory bronchiole. Although the conducting airways and alveolar regions have been well examined, morphological details of the respiratory bronchiole remain to be elucidated. To better understand the architecture of the respiratory bronchiole, we investigated this region of beagle dogs by means of serial sections of paraffin tissues. This study shows that respiratory bronchioles of beagle dogs consist of up to five generations. Branching patterns of the respiratory bronchiole of beagle dogs were comparable to those of humans. The surface of the respiratory bronchiole is comprised of the bronchiolar epithelial lining and alveolar outpocketings. The lining cells of beagle dogs are mainly nonciliated cells (Clara cells) whereas ciliated cells are very rare.
Animals↗
Viscoelastic properties of canine tracheal mucus: effects of structural inhomogeneities and storage.
Tracheal mucus is an inhomogeneous material and thus its viscoelastic properties may vary substantially within a mucus sample. In this study on canine tracheal mucus, we investigated this variation of mucus viscoelasticity and addressed the question whether or not the viscoelasticity is affected by storage of the mucus at low temperatures. Mucus samples were collected from 16 beagle dogs kept under clean air conditions. By means of magnetic rheometry, dynamic viscosity- and elasticity were determined either in the fresh state of these samples or after storage at -80 degrees C. Owing to inhomogeneities within the gel-structure of the mucus, local values of the viscoelastic parameters differed by more than an order of magnitude. Short storage periods (5 d) were found to decrease, long periods (100 d) to increase the viscosity as well as elasticity parameters of the mucus material. These results emphasize the fact that measured viscoelastic properties of mucus are average values depending on the measuring protocol. In addition, these values are modified by storage of the mucus at low temperatures.
Animals↗
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.
Adolescent↗
Prostanoids mediate IL-1beta-induced beta-adrenergic hyporesponsiveness in human airway smooth muscle cells.
We have previously reported that pretreatment of cultured human airway smooth muscle (HASM) cells with interleukin-1beta (IL-1beta) results in decreased beta-adrenergic responsiveness. The purpose of this study was to determine whether prostanoids released as a result of cyclooxygenase-2 (COX-2) induction by IL-1beta contribute to this effect of the cytokine. Confluent serum-deprived HASM cells were studied in passages 4-7. IL-1beta (20 ng/ml for 22 h) reduced the ability of the beta-agonist isoproterenol (Iso) to decrease stiffness of HASM cells as measured by magnetic twisting cytometry. The effect of IL-1beta on Iso-induced changes in cell stiffness was abolished by nonselective [indomethacin (Indo), 10(-6) M] and selective (NS-398, 10(-5) M) COX-2 inhibitors. Indo and NS-398 also inhibited both the increased basal cAMP and the decreases in Iso-stimulated cAMP production induced by IL-1beta. IL-1beta (20 ng/ml for 22 h) caused an increase in both basal (15-fold) and arachidonic acid (AA)-stimulated (10-fold) PGE2 release. Indo blocked basal and AA-stimulated PGE2 release in both control and IL-1beta-treated cells. NS-398 also markedly reduced basal and AA-stimulated PGE2 release in IL-1beta-treated cells but had no significant effect on AA-stimulated PGE2 release in control cells. Western blot analysis confirmed the induction of COX-2 by IL-1beta. Exogenously administered PGE2 (10(-7) M, 22 h) caused a significant reduction in the ability of Iso to decrease cell stiffness, mimicking the effects of IL-1beta. Cycloheximide (10 microg/ml for 24 h), an inhibitor of protein synthesis, also abolished the effects of IL-1beta on Iso-induced cell stiffness changes and cAMP formation. In summary, our results indicate that IL-1beta significantly increases prostanoid release by HASM cells as a result of increased COX-2 expression. The prostanoids appear to contribute to beta-adrenergic hyporesponsiveness, perhaps by heterologous desensitization of the beta2 receptor.
Bucladesine↗
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↗
Diagnosis of emphysema in patients with chronic bronchitis: a new approach.
Aerosol-derived airway morphometry (ADAM) and aerosol bolus dispersion (D) are altered in patients or animal models with lung emphysema. This study was performed to examine the sensitivity and specificity of ADAM and D in the detection of emphysema in vivo compared with conventional lung function parameters. The study comprised patients with chronic obstructive bronchitis (COB) without emphysema (group COB; n=19, age 56+/-8 yrs, forced expiratory volume in one second (FEV1)/vital capacity (VC) 66+/-12% predicted) and patients with chronic bronchitis with high-resolution computed tomography-confirmed emphysema (group COB-E; n=20), age 65+/-7 yrs, FEV1/VC 44+/-16% pred). Using monodisperse aerosol particles ADAM assessed the calibres of peripheral airspaces, while D measured convective gas mixing. Among all lung function parameters, ADAM and D showed the highest sensitivity and specificity for separating patients with COB from those with COB-E (area under the receiver operating characteristics curve (pROC) 0.99 and 1.0, respectively). In patients with COB aerosol parameters did not differ from those found in the control group, whereas patients with COB-E exhibited a two-fold increase in peripheral airspace dimensions compared with subjects with COB (0.86+/-0.07 versus 0.37+/-0.02 mm, p=0.0001) and an increase in D by >50% (541+/-74 versus 345+/-42 cm3, p=0.0001). In conclusion, aerosol-derived airway morphometry and aerosol bolus dispersion are powerful tools in the differential diagnosis of chronic obstructive pulmonary disease.
Administration, Inhalation↗
[Sick lungs despite better air quality?].
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Air Pollution↗
Detection of impaired intrapulmonary convective mixing by aerosol bolus dispersion in patients with emphysema.
The broadening of an inhaled aerosol bolus (aerosol bolus dispersion) during respiration provides a noninvasive, nonradioactive, and easy to perform technique which is a measure of the extent of convective gas mixing processes in the lung and symmetry of ventilation during the breathing cycle. In this study, this technique was evaluated for the ability to detect ventilation inhomogeneities in pulmonary emphysema (PE). An aerosol bolus undergoes changes in shape between its inspiration and expiration. In comparison with the inhaled bolus, the exhaled bolus is more spread because of convective mixing and may have a shift in the location of the mode caused by asymmetries of filling and emptying of lung units. We hypothesized that in PE these changes differ from healthy subjects and are related to lung health. Twenty nine patients with PE inhaled 25 ml boluses containing 0.9 micron monodisperse aerosol particles into volumetric lung depths of 200, 400, 600, and 800 cm3. The control group were 79 healthy subjects. As each bolus was expired, we measured bolus dispersion (volumetric width at one-half aerosol concentration peak height) and mode shift. In patients with PE exhaled boluses were significantly broader than those exhaled by normal subjects at all volumetric lung depths. At a lung depth of 800 cm3, patients showed a bolus dispersion that was 52% greater than that of healthy subjects (p < 0.0001) and they exhaled the bolus mode earlier (p < 0.0001). Aerosol bolus parameters were not influenced by anthropometric data. Pulmonary function parameters indicating obstruction showed a weak negative correlation with aerosol bolus parameters (R2 < 0.4). The bolus parameters appeared to be supplemental to conventional lung function tests and significantly indicated marked ventilation asymmetry and altered convective gas transport in pulmonary emphysema. The results support the use of the aerosol bolus dispersion test in assessing peripheral parenchymal lung injury.
Administration, Inhalation↗
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↗
Aerosol dispersion in human lung: comparison between numerical simulations and experiments for bolus tests.
Bolus inhalations of 0.87-micron-diameter particles were administered to 10 healthy subjects, and data were compared with numerical simulations based on a one-dimensional model of aerosol transport and deposition in the human lung (J. Appl. Physiol. 77: 2889-2898, 1994). Aerosol boluses were inhaled at a constant flow rate into various volumetric lung depths up to 1,500 ml. Parameters such as bolus half-width, mode shift, skewness, and deposition were used to characterize the bolus and to display convective mixing. The simulations described the experimental results reasonably well. The sensitivity of the simulations to different parameters was tested. Simulated half-width appeared to be insensitive to altered values of the deposition term, whereas it was greatly affected by modified values of the apparent diffusion in the alveolar zone of the lung. Finally, further simulations were compared in experiments with a fixed penetration volume and various flow rates. Comparison showed good agreement, which may be explained by the fact that half-width, mode shift, and skewness were little affected by the flow rate.
Aerosols↗
Respiratory effects are associated with the number of ultrafine particles.
The association between fine and ultrafine particles and respiratory health was studied in adults with a history of asthma in Erfurt, Eastern Germany. Twenty-seven nonsmoking asthmatics recorded their peak expiratory flow (PEF) and respiratory symptoms daily. The size distribution of ambient particles in the range of 0.01 to 2.5 microm was determined with an aerosol spectrometer during the winter season 1991-1992. Most of the particles (73%) were in the ultrafine fraction (smaller than 0.1 microm in diameter), whereas most of the mass (82%) was attributable to particles in the size range of 0.1 to 0.5 microm. Because these two fractions did not have similar time courses (correlation coefficient r = 0.51), a comparison of their health effects was possible. Both fractions were associated with a decrease of PEF and an increase in cough and feeling ill during the day. Health effects of the 5-d mean of the number of ultrafine particles were larger than those of the mass of the fine particles. In addition, the effects of the number of the ultrafine particles on PEF were stronger than those of particulate matter smaller than 10 microm (PM10). Therefore, the present study suggests that the size distribution of ambient particles helps to elucidate the properties of ambient aerosols responsible for health effects.
Air Pollutants↗
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.
Administration, Inhalation↗
[Pneumologic diagnosis with model aerosols--1: Intrapulmonary morphometry. Principles and initial results of clinical research].
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Aerosols↗
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↗
Morphometric evaluation of bronchial glands of beagle dogs.
Using lung tissues of beagle dogs, we developed a method for objective estimation of bronchial glands. Defined generations (5th, 10th, 15th and 20th) of bronchi were collected according to the microdissection method by Plopper et al. (1983) [1]. Transverse sections were prepared for both light microscopic and electron microscopic studies. The point counting using prints made by a video copy processor was performed for estimation of the volume density of bronchial glands. Bronchial glands were observed throughout the canine bronchial tree. Moreover, a distinct difference was found in the volume density of bronchial glands depending on the lobe examined and the generation number. Recently, we performed a long-term inhalation study using beagle dogs in order to elucidate toxic effects of sulfur(IV) and acidic sulfate aerosols (Heyder et al., 1994) [2]. In addition to the quantitative analysis of surface epithelia, the volume density of submucosal glands in the bronchial wall was measured according to the method described above. As preliminary result, there was a tendency to an increased volume density of glands in the exposure group. Detailed quantitative evaluation of bronchial glands may enable detection of finite changes induced by low level concentrations of air pollutants.
Air Pollutants↗