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J Heyder

Publications and source records attributed to J Heyder.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1996

Pharmacological activation changes stiffness of cultured human airway smooth muscle cells.

Using magnetic twisting cytometry (MTC), we measured the cytoskeletal stiffness of adherent human airway smooth muscle (HASM) cells. We hypothesized that modulation of actin-myosin interactions by application of contractile agonists would induce changes in cytoskeletal stiffness. In cells plated on high-density collagen, bradykinin (10(-6) M) and histamine (10(-4) M) increased stiffness by 85 +/- 15 and 68 +/- 16%, respectively. Increases in cell stiffness were also consistently observed after acetylcholine, substance P, and KCl. The bronchodilator agonists isoproterenol, prostaglandin E2, forskolin, dibutryl adenosine 3', 5'-cyclic monophosphate, and 8-bromoguanosine 3', 5'-cyclic monophosphate each caused a dose-dependent decrease in cell stiffness in unstimulated as well as bradykinin-treated cells. HASM cells plated on high-density collagen were stiffer than cells plated on low-density collagen (126 +/- 16 vs. 43 +/- 3 dyn/cm2) and developed more pronounced increases in stiffness in response to bradykinin as well as more pronounced decreases in stiffness in response to isoproterenol. These results are consistent with the hypothesis that modulation of actin-myosin interactions by application of contractile agonists causes changes in cytoskeletal stiffness of HASM cells. MTC may be a valuable tool for evaluating the mechanisms of pharmacomechanical coupling in airway smooth muscle cells in culture.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Long-term canine exposure studies with ambient air pollutants.

Dogs are often the species of choice as an experimental model for the study of pulmonary responses to long-term exposure to air pollutants in chambers simulating environmental or occupational exposure in man. Their lungs bear a reasonable resemblance to human lungs, they are large enough to allow serial measurements of pulmonary responses, and they live long enough to ensure that findings are not confounded by aging. Several long-term canine exposure studies with ambient air pollutants have been performed since 1957: seven studies with gaseous and particulate sulphur (IV); three studies with nitrogen oxides; three studies with ozone; two studies with acidic particles; three studies with mixtures of sulphurous pollutants that might have resembled the 1952 London smog; and one study in which raw and ultra violet (UV)-irradiated motor vehicle exhaust and sulphurous pollutants were used. The findings support the hypothesis that long-term exposure to air pollutants at ambient levels might cause bronchitic lesions (sulphur oxide), emphysematous lesions (nitrogen dioxide) or fibrotic lesions (ozone). None of the studies showed an indication of synergistic effects. To improve our understanding of pulmonary responses initiated by the inhalation of pollutants over long periods of time, new concepts are needed. Investigators should consider studies with canine models of cardiopulmonary diseases, the application of novel immunological and molecular biology techniques, the phenomena of tolerance and adaptation to inhaled air pollution, and exposure atmospheres with increasing complexity, including fine and ultrafine particles.

Air Pollutants↗
PubMed1995

Aerosol derived airway morphometry in healthy subjects.

Monodisperse aerosol particles can be used to non-invasively probe intrapulmonary airspace dimensions. In this study, the aerosol-derived airway morphometry technique was used to study airspace dimensions in 79 healthy subjects, in order to assess reference data for the future clinical application of aerosol-derived airway morphometry, and to investigate the effect of lung inflation, anthropometric, and lung function parameters on aerosol-derived airway morphometry. Intrapulmonary airspace dimensions were assessed by measuring the deposition of monodisperse, hydrophobic submicron aerosol particles during breathholding. Additionally, measurements of spirometric and body plethysmographic lung function were performed. Airspace dimensions were in good agreement with morphometric lung data. Airspace dimensions increased with increasing lung inflation. Interindividual variation of airspace dimensions was lowest in the lung periphery, at high levels of lung inflation, and when the volumetric lung depth was normalized to the end-inspiratory lung volume. Analysis of variance showed an increase of airspace dimensions with age. The results of this study indicate that aerosol-derived airway morphometry is dependent on the level of lung inflation and the age of the subject. These results suggest that in contrast to conventional lung function techniques, aerosol-derived airway morphometry might be a powerful tool for the detection of small changes in peripheral airway geometry.

Adult↗
PubMed1995

Peripheral airspace dimensions in patients with COPD.

Monodisperse aerosol particles can be used to assess noninvasively intrapulmonary airspace dimensions. Since emphysematic changes in the peripheral lung are difficult to detect with most of the common lung function tests, aerosol-derived airway morphometry was used to assess the peripheral airspace dimensions (EAD800) in 25 patients with COPD and in 36 healthy volunteers. Spirometric and body plethysmographic measurements were performed in all patients. In ten patients, high-resolution CT-derived mean lung density (MLD) was additionally assessed. In healthy subjects, EAD800 was 0.39 +/- 0.05 mm. In patients, EAD800 was significantly increased (0.82 +/- 0.33 mm). In a subset of nine patients with severe alpha 1-antitrypsin deficiency and clinically severe emphysema, EAD800 was even larger (1.14 +/- 0.32 mm). In patients, EAD800 correlated with MLD (r = 0.82), diffusion capacity (DCO) (r = 0.78), and FEV1 (r = -0.75). Since MLD is considered a valid indicator for lung emphysema, the close correlation between EAD800 and MLD suggests that EAD800 reflects enlarged peripheral airspace dimensions in patients with emphysema.

Adolescent↗
PubMed1995

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.

Aerosols↗
PubMed1994

Morphologic effects of a sulfur(IV) aerosol on the nasal cavity of beagle dogs.

Morphologic changes were observed in nasal cavities of beagle dogs after long-term exposure to a respirable sulfur(IV) aerosol at a concentration equivalent to a sulfur dioxide (SO2) concentration of 0.6 mg/m3. The changes were characterized by a thickened epithelial layer resulting from epithelial proliferation, by a loss of secretory material, and by moderate mononuclear cell infiltration.

Administration, Inhalation↗
PubMed1994

Pulmonary dead space and airway dimensions in dogs at different levels of lung inflation.

The quasi-stationary front that separates inspired gas from mixed alveolar gas is largely determined by the balance between diffusive and convective forces of gas transport. To investigate parameters influencing this balance, a study was performed on eight anesthetized ventilated beagle dogs. Measurements were made of the volume of pulmonary dead space corresponding to four end-inspiratory lung volumes. Aerosol recovery techniques were used to determine airway sizes at lung depths corresponding to those respective dead space volumes as well as at fixed volumetric depths between 70 and 250 ml. Mean dead space volumes as measured by a single inhalation of He (and SF6) were 112 +/- 15 (SD) ml (127 +/- 15 ml), 120 +/- 18 ml (137 +/- 20 ml), 127 +/- 18 ml (145 +/- 20 ml), and 133 +/- 19 ml (155 +/- 21 ml) at end-inspiratory lung volumes of 64, 71, 79, and 86%, respectively, of total lung capacity. At fixed lung depths the airway diameters increased with higher levels of lung inflation. However, airway diameters "at the end of the dead space" did not change significantly. They were approximately 0.5 mm for SF6 dead space and approximately 0.75 mm for He dead space. These findings support the theoretical prediction that the position of the diffusion front during breathing is strongly dependent on airway geometry and much less dependent on parameters of the breathing maneuver.

Animals↗
PubMed1994

Detection of early lung impairment with aerosol bolus dispersion.

The broadening of inhaled aerosol boluses (aerosol bolus dispersion) during respiration provides a noninvasive measure of convective gas mixing in the lungs. In this study, the sensitivity and specificity of this technique for the diagnosis of early lung impairment due to cigarette smoking was evaluated. Two hundred and sixteen randomly selected subjects (126 smokers and 90 nonsmokers) were investigated with aerosol dispersion in comparison to conventional lung function tests. The cumulative cigarette consumption of the subjects was quantified by "pack-years" (PY). Smokers were classified into the following groups: 0 < PY < or = 10; 10 < PY < or = 20; 20 < PY < or = 30; and PY > 30. Forced expiratory volume in one second (FEV1), maximal expiratory flow at 25, 50 and 75% vital capacity (MEF25, MEF50 and MEF75) decreased significantly with increasing cigarette consumption. In comparison to nonsmokers, FEV1 was significantly reduced in smokers of 10 < PY < or = 30, and MEF75 was significantly reduced in smokers of PY > 20. Aerosol bolus dispersion increased with increasing PY. For all groups of smokers, even those with PY < 10, bolus dispersion was significantly increased in comparison to lifelong nonsmokers, indicating alterations in convective gas mixing in the lungs. Calculation of receiver operating characteristics for the lung function parameters under consideration showed that bolus dispersion has a higher sensitivity and specificity than conventional lung function parameters. Hence, the aerosol bolus dispersion test could be a promising epidemiological tool to study early abnormalities in intrapulmonary gas mixing due to environmental factors.

Adult↗
PubMed1992

Convective and diffusive gas transport in canine intrapulmonary airways.

The significance of convective and diffusive gas transport in the respiratory system was assessed from the response of combined inert gas and particle boluses inhaled into the conducting airways. Particles, considered as "nondiffusing gas," served as tracers for convection and two inert gases with widely different diffusive characteristics (He and SF6) as tracers for convection and diffusion. Six-milliliter boluses labeled with monodisperse di-2-ethylhexyl sebacate droplets of 0.86-microns aerodynamic diameter, 2% He, and 2% SF6 were inspired by three anesthetized mechanically ventilated beagle dogs to volumetric lung depths up to 170 ml. Mixing between inspired and residual air caused dispersion of the inspired bolus, which was quantified in terms of the bolus half-width. Dispersion of particles increased with increasing lung depth to which the boluses were inhaled. The increase followed a power law with exponents less than 0.5 (mean 0.39), indicating that the effect of convective mixing per unit volume was reduced with depth. Within the pulmonary dead space, the behavior of the inert gases He and SF6 was similar to that of the particles, suggesting that gas transport was almost solely due to convection. Beyond the dead space, dispersion of He and SF6 increased more rapidly than dispersion of particles, indicating that diffusion became significant. The gas and particle bolus technique offers a suitable approach to differential analysis of gas transport in intrapulmonary airways of lungs.

Animals↗
PubMed1991

Aerosol-derived lung morphometry: comparisons with a lung model and lung function indexes.

This study evaluated the ability of aerosol-derived lung morphometry to noninvasively probe airway and acinar dimensions. Effective air-space diameters (EAD) were calculated from the time-dependent gravitational losses of 1-microns particles from inhaled aerosol boluses during breath holding. In 17 males [33 +/- 7 (SD) yr] the relationship between EAD and volumetric penetration of the bolus into the lungs (Vp) could be expressed by the linear power-law function, log (EAD) alpha beta log (Vp). Our EAD values were consistent with Weibel's symmetric lung model A for small airways and more distal air spaces. As lung volume increased from 57 to 87% of total lung capacity (TLC), EAD at Vp of 160 and 550 cm3 increased 70 and 41%, respectively. At 57% TLC, log (EAD) at 160 cm3 was significantly correlated with airway resistance (r = -0.57, P less than 0.0204) but not with forced expired flow between 25 and 75% of vital capacity. Log (EAD) at 400 cm3 was correlated with deposition of 1-micron particles (r = -0.73, P less than 0.0009). We conclude that aerosol-derived lung morphometry is a responsive noninvasive probe of peripheral air-space diameters.

Adult↗
PubMed1989

Effect of cystic fibrosis on inhaled aerosol boluses.

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, may have a shift in the location of the mode caused by asymmetries of filling and emptying of lung units, and contains fewer particles because of particle deposition. We hypothesized that the extent of these changes is related to lung health. To examine this, 11 patients with cystic fibrosis (CF) and 11 healthy subjects inhaled 70 cm3 boluses containing 1 micron monodisperse particles that were inspired to volumetric penetrations (Vp) of 100 to 700 cm3. As each bolus was expired, we measured spreading (volumetric width at one-half aerosol concentration peak height), modal shift, and particle deposition. Patients with CF exhaled boluses that were broader than those exhaled by normal subjects at all penetrations examined. At a Vp of 600 cm3, patients had a mean bolus half-width that was 68% greater than that of healthy subjects (p less than 0.0001), and they exhaled the bolus mode 20% earlier (p less than 0.0002). Particle deposition was increased compared with that in normal subjects at all Vp. For example, mean deposition at a Vp of 600 cm3 was 46.2 +/- 2.6% (SE) for the patients versus 25.8 +/- 1.6% for the normal subjects (p less than 0.0001). Among the patients with CF, pulmonary function parameters indicating obstruction were significantly correlated with bolus spreading and aerosol deposition: the percent predicted FEV1/FVC was inversely correlated with spreading (r = -0.88, p less than 0.0004) and deposition (r = -0.84, p less than 0.0008).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1988

Convective mixing in human respiratory tract: estimates with aerosol boli.

Convective gas mixing in the respiratory tract of 17 healthy male subjects was studied by an aerosol bolus technique. The monodisperse 1 micron di(2-ethylhexyl)sebacate droplets we used behaved as a nondiffusing gas. As the bolus was inspired to different depths and then expired, we measured the extent to which the bolus spread. We found that the deeper the bolus penetrated into the lungs, the more it became dispersed. The half-width of the expired bolus was a linear function of the volume to which the bolus penetrated at volumetric penetrations of 100-800 cm3. This suggests that convective mixing is not confined to central airways but can also occur in the lung periphery.

Adult↗
PubMed1983

Charting human thoracic airways by aerosols.

A non-invasive method is described which permits the estimation of average airway calibre as a function of the volumetric depth in the human respiratory tract. It is based upon the measurement of gravitational particle losses during breath-holding from boli of monodisperse aerosols inspired to different depths in the respiratory tract. Aerosol boli comprising particles of 1.5 microns aerodynamic diameter and 45 microns settling velocity were inspired to depths between 80 and 820 cm3. The number of particles recovered decreased exponentially with the period of breath-holding, and an average airway radius was calculated for each lung depth from the slope of these exponential functions. The average airway radius changes rapidly with depth. Among six subjects it varies between 630 and 1400 microns at 120 cm3 lung depth and between 165 and 280 microns at 600 cm3 lung depth. The average airway radii evaluated in this study are within the range covered by current lung models.

Aerosols↗
PubMed1982

Alveolar deposition of inhaled particles in humans.

Total deposition data were used to estimate the efficiency of the alveolar region of the human respiratory tract to collect aerosol particles. When inspired at a flow rate of 250 cm3s-1 (1000 cm3s-1) through the mouth particles of 2.6 micrometers (1.7 micrometer) aerodynamic diameter are the largest particles which pass through the extrathoracic and bronchial region without being deposited. They are deposited in the alveolar region only.

Aerosols↗
PubMed1982

Particle transport onto human airway surfaces.

Three domains can be distinguished for particle transport onto human airway surfaces: 1. thermodynamic domain. Particles are transported by diffusion. Deposition decreases with particle diameter, is independent of particle density, increases with inspiration time and should be independent of flow rate. 2. intermediate domain. Particles are transported by diffusion and gravitational sedimentation. Deposition is slightly dependent on particle diameter, particle density and flow rate and increases with inspiration time. Since particles are effectively collected by inertial impaction in the nose this domain disappears for nose-breathing. 3. aerodynamic domain. Particles are transported by gravitational sedimentation and by inertial impaction. Deposition increases with particle diameter, particle density, inspiration time and flow rate. For normal breathing this domain consists of three subdomains. 3.1. sedimentation domain. Particles aerodynamically smaller than 2 micrometers are deposited by gravitational sedimentation in the alveolar region. 3.2. impaction-sedimentation domain. Particles aerodynamically between 2 and 12 micrometers are deposited by inertial impaction in the extrathoracic airways, by gravitational sedimentation and inertial impaction in the bronchial airways and by gravitational sedimentation in the alveolar region. 3.3 impaction domain. Particles aerodynamically larger than 12 micrometers are deposited by inertial impaction predominantly in the extrathoracic and less in the bronchial airways.

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↗