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Biomedical subjects

G Scheuch

Publications and source records attributed to G Scheuch.

At least 37 records · Page 2Linked 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

Intrapulmonary distribution of deposited particles.

Inhalation drug delivery for both topical and systemic treatments has many advantages over oral, intravenous, or subcutaneous drug delivery. Because some drugs should be deposited within the bronchial tree and others should deposit within the respiratory zone of the lung, it should be possible to determine and influence the preferential site of drug deposition to develop efficient inhalation therapy strategies. In this article, a method that allows estimation of the longitudinal distribution of deposited particles in the lungs of individual subjects is introduced. From the photometrically measured deposition of monodisperse di-2-ethylhexyl sebacate (DEHS) droplets, the longitudinal distribution of deposited particles (i.e., the number of particles that are deposited in a certain lung volume element) can be assessed. In this study in four healthy volunteers the distribution of deposited particles was assessed for different airflow rates, tidal volumes (VTS), and particle sizes. The results showed that there are considerable differences in the longitudinal distribution of deposited particles between subjects and that the distribution is strongly dependent on particle size: if particle size is increased, the site of particle deposition is shifted proximally. Particles with diameters greater than approximately 5 microns cannot penetrate to a volumetric lung depth (VP) greater than approximately 600 cm3 even if the VT is increased. Airflow rate has a minor effect on the distribution of deposited particles, but if airflow rate increases, the site of particle deposition is slightly shifted peripherally. This method can be used to investigate individual patterns of drug deposition in human lungs noninvasively and to develop and optimize inhalation strategies for inhalation drug delivery.

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↗
PubMed1999

In vivo characterization of the transitional bronchioles by aerosol-derived airway morphometry.

Effective airway dimensions (EADs) were determined in vivo by aerosol-derived airway morphometry as a function of volumetric lung depth (VLD) to identify and characterize, noninvasively, the caliber of the transitional bronchiole region of the human lung and to compare the EADs by age, gender, and disease. By logarithmically plotting EAD vs. VLD, two distinct regions of the lung emerged that were identified by characteristic line slopes. The intersection of proximal and distal segments was defined as VLD(trans) and associated EAD(trans). In our normal subjects (n = 20), VLD(trans) [345 +/- 83 (SD) ml] correlated significantly with anatomic dead space (224 +/- 34 ml) and end of phase II of single-breath nitrogen washout (360 +/- 53 ml). The corresponding EAD(trans) was 0.42 +/- 0. 07 mm, in agreement with other ex vivo measurements of the transitional bronchioles. VLD(trans) was smaller (216 +/- 64 ml) and EAD(trans) was larger (0.83 +/- 0.04 mm) in our patients with chronic obstructive pulmonary disease (n = 13). VLD(trans) increased with age for children (age 8-18 yr; P = 0.006, n = 26) and with total lung capacity for age 8-81 yr (P < 0.001, n = 61). This study extends the usefulness of aerosol-derived airway morphometry to in vivo measurements of the transitional bronchioles.

Adolescent↗
PubMed1999

Increased fine particle deposition in women with asymptomatic nonspecific airway hyperresponsiveness.

Previous studies suggest that lung function tests using monodisperse aerosols can help to identify early stages of lung diseases. We investigated intrapulmonary particle loss and aerosol bolus dispersion-a marker of convective gas transport-in 32 women with asymptomatic nonspecific bronchial hyperresponsiveness (BHR) compared with 60 women without BHR. Deposition of inhaled particles (0.9 micrometer mass median aerodynamic diameter [MMAD]) was calculated from particle losses of inhaled aerosol boluses consisting of di-2-ethylhexyl sebacate droplets. Convective gas mixing was assessed by the aerosol bolus dispersion method. Women with BHR, nonsmokers as well as smokers, showed significantly increased deposition of aerosol particles (nonsmokers: 45.6 +/- 8.8%; smokers: 49.2 +/- 5.4%; mean +/- SD) compared with the control group of female nonsmokers without BHR (38.2 +/- 9.1%; mean +/- SD) (p < 0.01). Aerosol bolus dispersion values showed a trend for higher values in subjects with BHR (nonsmokers: 572 +/- 122 cm3; smokers: 587 +/- 85 cm3) compared with the control group (542 +/- 88 cm3) (p = 0.2). Also, the maximal expiratory flow at 25% vital capacity (MEF25) showed a trend for decreased values in nonsmokers with BHR compared with nonsmokers without BHR (64 +/- 16% of predicted versus 78 +/- 24% of predicted; p = 0.03). These results suggest that deposition of inhaled particles (0.9 micrometer MMAD) administered by the aerosol bolus technique is a sensitive index of peripheral lung injury that is usually not assessable by conventional methods.

Adult↗
PubMed1999

Noninvasive diagnosis of emphysema. Aerosol morphometry and aerosol bolus dispersion in comparison to HRCT.

Aerosol-derived airway morphometry (ADAM) and aerosol bolus dispersion (ABD) test are altered in patients with emphysema. We examined the diagnostic power of these aerosol methods in comparison with the noninvasive "gold-standard" HRCT in 50 consecutive patients with various lung diseases. The severity of airflow limitation was mild to moderate in the group of patients without emphysema and moderate to severe in the group of patients with HRCT-confirmed emphysema (FEV(1), 78 +/- 23% pred versus 53 +/- 33% pred; p < 0. 001). Among all lung function parameters under consideration ADAM showed the highest sensitivity and specificity for separating patients with emphysema from those without emphysema (area under the operating characteristics curve: p(ROC), 0.92), followed by ABD (p(ROC), 0.90), a marker for ventilation inhomogeneities. In patients with HRCT-confirmed macroscopic emphysema, peripheral air-space dimensions (EAD) at a relative volumetric lung depth V(pr) of 0.20 measured by ADAM were 155% larger, and bolus dispersion (ABD) at a lung depth of V(p) 600 ml was 53% larger than those observed in patients with other lung diseases (EAD = 0.84 +/- 0.53 mm versus 0.33 +/- 0.10 mm, p < 0.0001; ABD = 706 +/- 154 cm(3) versus 462 +/- 109 cm(3); p < 0.0001). EAD showed a significant correlation with the HRCT visual score (r = 0.78, p = 0.01). ABD showed weak significant correlations with all HRCT parameters under consideration (visual score, pixel density, mean lung density) (r = 0.45 to 0.66; p < 0.05). ADAM and ABD are powerful tools for the noninvasive diagnosis of macroscopic emphysema.

Aerosols↗
PubMed1999

[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↗
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↗
PubMed1998

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↗
PubMed1997

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↗
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↗
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↗
PubMedDate not supplied

Alveolar deposition of monodisperse aerosol particles in the lung of patients with chronic obstructive pulmonary disease.

Knowledge about the regional deposition of aerosol particles is essential in order to perform efficient inhalation therapy or to minimize health risks due to environmental or occupational aerosol particles. In this study, 2 techniques were used to measure thoracic deposition and to differentiate between bronchial and alveolar deposition. The first technique was the clearance-derived regional deposition (CRD) technique and the second the single-breath regional deposition (SBRD) technique. Deposition was measured in 12 patients with alpha1-antitrypsin deficiency and symptoms of moderate to severe chronic obstructive pulmonary disease (COPD) using monodisperse test particles with aerodynamic diameters of 2, 3, and 4 microm. In CRD, the kinetic of particle clearance within the first 24 hours after inhalation was used to determine bronchial and alveolar deposition. In SBRD, the longitudinal distribution of deposited inert test particles was used to calculate the particle fraction deposited within and distal to the dead space. Both techniques delivered very similar mean values for total and alveolar deposition. Due to controlled slow and deep inhalations, alveolar deposition was as much as 50%. Therefore, SBRD can be considered as an easy tool to study alveolar deposition in patients.

Aerosols↗
PubMedDate not supplied

Pulmonary deposition of monodisperse aerosols in patients with chronic obstructive pulmonary disease.

In order to improve patient convenience and drug availability for patients with alpha 1-protease inhibitor deficiency, the administration via the inhalation route has been considered. This study investigated if it is possible to obtain high values of peripheral aerosol deposition by using optimized and controlled inhalation conditions. Therefore, peripheral deposition was studied in 10 patients with alpha 1-protease inhibitor deficiency (phenotype PiZ) and moderate to severe chronic obstructive pulmonary disease by measuring the 24-hour Clearance of radiolabeled inert iron oxide particles with diameters of 2 microns, 3 microns, and 4 microns. Patients inhaled a large volume of aerosol (1000 to 2000 cm3), which was normalized to the individual lung function, with a flow rate of 200 cm3/S. Due to this breathing pattern, peripheral deposition was for all particle sizes above 50% of the inhaled aerosol. The highest peripheral deposition (68%) was found for 3-microns particles.

Administration, Inhalation↗
PubMedDate not supplied

Effect of heart rate on aerosol recovery and dispersion in human conducting airways after periods of breathholding.

With a newly developed aerosol inhalation device, small volumes of aerosols ("boluses") can be inspired predominantly into the conducting airways of the human lungs. The aerosol is injected by a fast-operating valve system using preselected volumes near the end of a clean air inhalation of 1000 cm3. Particle behavior in upper human airways was investigated by measuring particle recovery and bolus dispersion in exhaled air with a laser photometer positioned directly in front of the mouth after various periods of breathholding. The effect of physical motion of the heart on these measurements has been investigated by increasing the heart rate of a subject by more than a factor of 2. Monodisperse sebacate aerosols were used with droplets in the aerodynamic size (dac) range between 0.8 and 1.1 micron to minimize particle losses by diffusion and by inertial forces. It was shown that motion of the heart considerably influences both particle recovery and dispersion of such boluses during postinhalation periods of breathholding. For a twofold enhancement in heart frequency the standard deviation of the expired aerosol bolus was increased by up to 60% after certain breathholding periods. Particle recovery from shallow volumetric lung depths was significantly decreased.

Aerosols↗