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Biomedical subjects

G Scheuch

Publications and source records attributed to G Scheuch.

At least 19 recordsLinked to original sources
PubMed2006

[Comparison of unspecific bronchial provocation during controlled and spontaneous inhalation].

Using controlled breathing patterns during inhalation of drugs is characterized by a high dose reproducibility which may be of advantage for bronchial provocation testing. In this study 30 healthy subjects with an anamnesis of atopy underwent in a randomized cross-over design bronchial provocation testing with methacholine either with the Viasys-Jäger-APS system or with controlled inhalations (AKITA-System) (controlled inhalation volume and flow). Measured was the frequency of positive test results. Positive test results were defined by a 20 % decline of FEV (1) or a 100 % increase of specific airway resistance (sRaw). There were no significant differences in the prevalence of positive test results obtained with both techniques: APS-FEV (1) : 8, AKITA-FEV (1) : 9; APS-sRaw: 18, AKITA-sRaw: 17. More subjects showed a 100 % increase of sRaw as compared to a 20 % decrease of FEV (1), which may be interesting in order to understand differences in the diagnostic information given by both parameters. However, there were some discrepancies: only in 25 of 30 cases (sRaw: 21 of 30 cases) the results (positive or negative) agreed between both techniques. Although the two techniques for bronchial provocation test showed some discrepancies, these data suggest that controlled inhalations may be an alternative to the APS-system.

Bronchial Provocation Tests↗
PubMed2005

Optimum peripheral drug deposition in patients with cystic fibrosis.

In order to identify the optimum particle size and breathing pattern for high peripheral deposition of inhaled drugs in patients with cystic fibrosis, regional deposition in these patients was studied systematically as a function of particle size, inhalation volume and flow rate. Regional deposition was assessed using the single-breath regional deposition technique in which the concentration profile of inhaled and exhaled non-radioactive, monodisperse test particles is analyzed. Using this technique particle deposition within the functional dead space volume and peripherally can be assessed. Regional deposition was measured in 12 patients with cystic fibrosis using 2, 3, 4, and 5.5 microm particles, inhalation volumes of 500, 1000, 1500, and 2000 cm(3), and inhalation flow rates of 100, 250, 500, and 750 cm(3)/sec. Peripheral deposition was highest when 2-3-microm particles were inhaled with air-flow rates of 250-500 cm(3)/sec. With these parameters peripheral deposition increased with increasing inhalation volume and reached values of about 60% of the total drug inhaled. It has been shown that high peripheral drug deposition can be achieved in patients with CF when inhalations are performed using an optimized combination of particle size and breathing pattern.

Administration, Inhalation↗
PubMed2004

[Inhaled antibiotic therapy in bronchiectasis?].

Antimicrobial therapy is an important aspect of disease management for patients with bronchiectasis. Delivery of an inhaled antibiotic is an appealing alternative to oral or intravenous administration because the antibiotic is delivered in high concentrations directly to the site of infection, eliminating the need for high systemic concentrations and reducing the risk of systemic toxicity. In recent controlled studies these potential benefits have been assessed in patients with bronchiectasis who became colonized by P. aeruginosa and the results support the use of nebulized antibiotics. In up to one-third of patients P. aeruginosa was eradicated from their sputum by inhaled antibiotic therapy and up to 62 % of patients showed improved medical condition. The further development of new aerosol devices supported by clinical testing will allow effective management of patients with bronchiectasis by an inhalation therapy that minimizes time constraints and drug loss which may improve health status and quality of life.

Administration, Inhalation↗
PubMed2004

Deposition of Foradil P in human lungs: comparison of in vitro and in vivo data.

In order to characterize the efficacy of dry powder inhalers, in vitro measurements are much easier to perform than human deposition studies, especially in early stages of drug development. In this study, lung deposition and delivered dose of radiolabeled Foradil P inhaled with the Aerolizer were measured in 10 healthy subjects. These data were then compared with data derived from an in vitro assessment of the device output and particle size distribution combined with mathematical modeling of lung deposition (modified ICRP-model). Delivered dose and lung deposition increased slightly but statistically significant with the inhalation peak flow in both the in vivo data and the in vitro data. The delivered dose ranged from 60% to 80% and lung deposition, relative to the fill weight, from 13% to 28%. Differences between the in vitro and in vivo data were slight and statistically not significant. This study indicates that in vitro assessment of device performance, in combination with lung deposition delivery data, are in good agreement with deposition data measured in healthy subjects. Since there was only a slight flow rate dependency of lung deposition without clinical relevance, it may additionally be concluded that the Aerolizer is a robust, easy to handle inhalation device with stable and reproducible drug delivery characteristics.

Administration, Inhalation↗
PubMed2003

[Difficulties in controlled inhalation of alpha 1-protease inhibitor].

In this paper a number of studies will be summarized which were designed to improve the inhalation of alpha 1 -protease inhibitor in patients with alpha 1-protease inhibitor deficiency. A pilot study has shown that the high inter-individual variability of drug deposition in the lungs is due to heterogeneous breathing patterns of the patients. Controlling the breathing pattern led to a significantly decreased variability. Then it was studied which particle size and breathing pattern resulted in highest peripheral lung deposition in patients with emphysema. It was found that for 3 - 4 microm particles and slow inhalation flow rate the peripheral deposition increases with increasing inhalation volume. After the development of an inhalation device which allows to perform controlled inhalations in clinical practice it was shown that this device, in combination with a breathing pattern individually normalized to the patients lung function, allows to deposit nearly 60 % of the drug into the patients lung periphery.

Administration, Inhalation↗
PubMed2003

[Controlled inhalation of beta2-sympaticomimetica after bronchial provocation].

The results of several studies indicate that controlling the breathing pattern (inhaled volume and flow rate) during inhalation increases the efficacy of drug delivery to the lungs. By inhaling slowly, deeply and under controlled conditions, intrapulmonary deposition of aerosol and its reproducibility can be increased. However, it has not yet been proven that such inhalations are well tolerated by patients, especially those with airway obstructions. In this study 12 patients with mild asthma underwent a bronchial provocation test. The following broncholysis was performed with controlled, slow, and deep inhalation using the AKITA-device. The patients were asked about the convenience of this inhalation using a questionnaire. In 80 % the controlled inhalation was judged as convenient, neither as too slow nor as too fast, neither as too deep nor as too shallow. Thus it turned out that controlled deep and slow inhalations are convenient even for patients with mild airway obstruction.

Administration, Inhalation↗
PubMed2003

Can aerosol-derived airway morphometry detect early, asymptomatical lung emphysema?

The aerosol-derived airway morphometry technique (ADAM) can be used to assess non-invasively peripheral airspace dimensions. It has been shown that this technique can identify permanent peripheral airspace enlargement in patients with lung emphysema, but it is yet unknown if early stages of emphysema can be detected. In this study, 89 aluminum welders were investigated. Although all (except two subjects) showed normal spirometry, in 29% of the subjects visual signs of early emphysema were observed with high-resolution computed tomography (HRCT) in a previous study. Using the ADAM technique, 28% of the subjects showed increased peripheral airspace dimensions. However, both groups with positive findings overlapped only in about half of the cases. Peripheral airspace dimensions correlated significantly with the mean lung density calculated from the HRCT scans, and lung density was significantly decreased in the group with increased airspace dimensions. The poor overlap of the positive findings observed with both techniques can be explained if it is considered that the visual HRCT technique and ADAM focus on different aspects of emphysematous changes in the lungs. Whereas visual HRCT is a powerful tool to identify focal changes in lung density but cannot detect mild homogeneous emphysema, ADAM delivers a measure for homogeneously distributed emphysema but cannot detect focal emphysema or regions with emphysema which are badly ventilated. Since ADAM is easy to perform, non-invasive, and can be repeatedly applied to human subjects without radiological concerns, this technique might become a useful tool for the detection and monitoring of lung emphysema in occupational medicine, epidemiology, and pharmaceutics.

Adult↗
PubMed2003

Peripheral deposition of alpha1-protease inhibitor using commercial inhalation devices.

Patients with hereditary alpha1-proteinase inhibitor (alpha1-PI) deficiency are at risk of developing lung emphysema. To prevent the development of this disease, alpha1-PI replacement therapy via inhalation may be a more convenient and effective therapy than the intravenous administration of the drug. In order to optimise this treatment approach, lung deposition of inhaled radiolabelled alpha1-PI (Prolastin) was studied using four different commercial inhalation devices (PARI-LC Star, HaloLite, and AKITA system in combination with LC Star and Sidestream) in six patients with alpha1-PI deficiency and mild-to-severe chronic obstructive pulmonary disease. The time required to deposit 50 mg of the Prolastin (5% solution) in the lung periphery was used as a measure for the efficiency of delivery. The time was calculated from measurements of total and peripheral lung deposition of the radiolabelled alpha1-PI. This time was shortest for the AKITA system (18-24 min) and significantly higher for the PARI-LC Star (44 min) and the HaloLite (100 min). The higher efficiency of drug delivery using the AKITA system is due to the fact that this device controls breathing patterns, which are optimised for each patient individually.

Administration, Inhalation↗
PubMed2002

Inhalation of aerosolized vitamin a: reversibility of metaplasia and dysplasia of human respiratory epithelia -- a prospective pilot study.

The objective of this preliminary uncontrolled study was twofold: First, to assess the feasibility of retinyl palmitate inhalation and second, to analyze the changes of metaplastic lesions of the respiratory epithelium (metaplasia or dysplasia) following retinyl palmitate inhalation. The response to a daily dose of 18.000 I.U. retinyl palmitate by inhalation over a period of 3 month was assessed in 11 subjects (9 smokers, 2 ex-smokers). Using white-light bronchoscopy combined with autofluorescence bronchoscopy, bronchial biopsies were taken before and after a 3 month-period. The biopsy samples were evaluated blind by a referee lung pathologist. The overall response rate (remission or partial remission) was 56% (95% CI 0.30 0.79; p<0.05). These data suggest that inhalation of retinyl esters could be a promising therapeutical approach for chemoprevention of lung cancer. Vitamin A; chemoprevention; lung cancer; squamous metaplasia; dysplasia; retinoids

Administration, Inhalation↗
PubMed2002

Mass output and particle size distribution of glucocorticosteroids emitted from different inhalation devices depending on various inspiratory parameters.

Efficient inhalation therapy depends on successful delivery of the drug to the lung. The efficacy of drug delivery is not only influenced by the characteristics of the inhalation device, but also by the patient's handling of the device and by the inspiratory maneuver achieved through the device. We analyzed the output characteristics of three different chlorofluorocarbon (CFC)-free breath-actuated inhalers for inhaled glucocorticosteroids (BUD Turbohaler, FP Diskus/Accuhaler and HFA-BDP Autohaler, respectively). Mass output and particle size distribution of drug aerosol delivered by the inhalers were determined depending on different inhalation parameters in vitro using an Andersen cascade impactor. We found that, beside the peak inspiratory flow (PIF), other factors such as flow acceleration and inhalation volume also have significant effects on aerosol generation with respect to mass output and particle size distribution. Thus, these parameters should be taken into account when a suitable device for an individual patient is to be selected. The dependency on inspiratory parameters was most pronounced for the dry powder inhalers. The Turbohaler showed by far the highest variance in particle output (fine particle fraction ranging from 3.4% to 22.1% of label claim), whereas the Diskus was less dependent on variations in inhalation (10.6% to 18.5% of label claim). The most constant aerosol output was found for the Autohaler, which also released the highest fine particle fraction (43.1% to 56.6% of label claim).

Administration, Inhalation↗
PubMed2002

In vitro testing of two formoterol dry powder inhalers at different flow rates.

The efficiency of two different dry powder inhaler systems for the application of the beta2-sympathomimetic drug Formoterol in the lungs has been tested in vitro. Particle size distributions for each device have been measured at four different flow rates (28.3, 40, 60, and 80 L/min) using an Andersen-Impactor. Mass median aerodynamic diameters (MMAD) of the dispersed powder and deposition of the drug in the respiratory tract was determined using a semiempirical lung deposition model. The optimum output for both devices determined by in vitro measurements is supposed to be achieved with flow rates of 40-60 L/min. The Oxis Turbuhaler delivers the smaller particles as the Foradil P Aerolizer and, thus, the Formoterol deeper into the lungs, but the high specific airflow resistance will influence the ability of patients with severe asthma and children to use the system.

Adrenergic beta-Agonists↗
PubMed2001

Comparison of clearance of particles inhaled with bolus and extremely slow inhalation techniques.

Ten healthy nonsmokers inhaled 6-microm (aerodynamic diameter) Teflon particles labelled with 111In twice, once with the shallow bolus technique (volumetic lung depth 76+/-20 mL ([+/- SD]) and once with the extremely slow inhalation technique (0.05 L/s). The radioactivity in the lungs was measured at 1 and 24 hours as well as at 1, 2, and 3 weeks after both inhalations. The 24-hour lung retention a percentage of lung deposition was significantly lower for the bolus inhalation, 46%+/-9% (+/- SD) than for the extremely slow inhalation, 56%+/-11%. The retention after 21 days as a percentage of the 24-hour retention was 55%+/-9% for the shallow bolus inhalation and 56%+/-10% for the extremely slow inhalation. Also within the subjects, clearance was similar for the 2 modes of inhalation. Deposition of particles inhaled with the 2 modes of inhalation was calculated with 2 model, one being based on Monte (Carlo particle transport together with an asymmetric lung model. Deposition predicted with this model agreed well with the experimental data under the assumption that there are large retained fractions only in small ciliated airways (bronchioli) and not in large ones. For the bolus inhalation, the model predicted 43% to 50% deposition in the bronchial (BB) region of initial lung deposition, 33% to 38% in the bronchiolar (bb) region, and 16% to 22% in the alveolar region. For the extremely slow inhalation, the model predicted 31% to 34% deposition in the BB region, 45% to 47% in the bb region, and 21% to 22% in the alveolar region. In addition, it predicted about the same ratio between bb and alveolar depositions for the 2 modes of inhalation. Thus, both the experimental and theoretical data indicate that the shallow bolus particles to a considerable extent reach both the bb and the alveolar regions and that they do that at about the same extent as the particles inhaled extremely slow. This conclusion is concerning the experimental data based on the assumption that there are no large retained fractions in the BB region. Another interpretation of the similar clearance for the two modes of inhalation is that there are large retained fractions in both the BB and the bb regions and that individual charactristics of clearance of these fractions are of importance rather than the site of deposition.

Administration, Inhalation↗
PubMed2001

Impulse oscillometry in healthy nonsmokers and asymptomatic smokers: effects of bronchial challenge with methacholine.

The clinical application of respiratory impedance measurements by oscillation techniques for monitoring bronchial challenge testing is hampered by the fact that data in healthy nonsmokers and asymptomatic smokers are very limited. The objective of this study was to analyze the changes in impedance to a methacholine provocation test in healthy nonsmokers and asymptomatic smokers, and to investigate whether smokers show a different response compared to nonsmokers. The response to methacholine challenge was assessed by impulse oscillometry (IOS) (resistance R and reactance X at 5, 10, 15, 20, 25, and 35 Hz) and spirometry (FEV1, MEF50) in 105 healthy subjects (55 nonsmokers: "NS"; 50 asymptomatic smokers: "S") in whom the provocation dose of 2.44 mg methacholine did not result in a fall of FEV1 below 20% predicted of the baseline value. The baseline reactance X values of S were significantly lower compared to NS from 10 to 35 Hz (p < or = 0.01), whereas S and NS did not differ in resistance R over the whole frequency spectrum from 5 to 35 Hz. S showed a significantly higher mean baseline resonant frequency X(f0); i.e., the frequency at which inertial forces are equal and opposite to elastic forces, compared to NS (NS: X(fo) = 10.8+/-2.9 Hz; S = 12.6+/-4.0 Hz, p = 0.01). In both groups methacholine challenge resulted in an increase in R (f) especially at 5 and 10 Hz, and a marked decrease in X(f) over the whole frequency spectrum. In S a significantly higher decrease of postchallenge X5Hz and X10Hz was measured compared to NS (NS: deltaX(5Hz) = -0.044+/-0.003; S: deltaX(5HZ) = -0.083+/-0.013; p = 0.0017. NS: deltaX(10Hz) = -0.050+/-0.001; S: deltaX(10Hz) = -0.082+/-0.017; p = 0.008). R and X at low frequencies showed a three to four times higher postchallenge reaction compared to FEV1. Pre- and postchallenge FEV1 did not correlate with resistance R (f) and reactance X(f) over the whole frequency spectrum. In S perchallenge X(f) values from 10 to 35 HZ were significantly lower, and postchallenge decrease of X5Hz and X10Hz values were significantly higher compared to that of NS, whereas pre- and postchallenge R(f) values were similar in both groups. These results can be explained by changes in the elastic properties of the lung induced by a diffuse subclinical respiratory bronchiolitis.

Adult↗
PubMed2001

[Biophysical basics of aerosol therapy in bronchial asthma].

For an effective inhalation therapy with aerosols the drug itself but also the inhalation device have to be considered. Several biophysical parameters influence the deposition in different regions of the respiratory tract. Particle size and the breathing pattern of the patient are the most important factors and have to be considered.

Aerosols↗
PubMed2000

Aerosol morphometry and aerosol bolus dispersion in patients with CT-determined combined pulmonary emphysema and lung fibrosis.

The simultaneous occurrence of pulmonary fibrosis and emphysema may present considerable problems in clinical assessment. Recent studies have shown that Aerosol Derived Airway Morphometry (ADAM) and Aerosol Bolus Dispersion (ABD) are changed in patients with pulmonary emphysema. This study was performed to assess the effect of simultaneous lung fibrosis in patients with emphysema on ADAM and ABD. ADAM and ABD measurements were performed in 20 patients with lone high resolution CT scan (HRCT) confirmed emphysema (E), and compared to those in 15 emphysematics with HRCT-confirmed superimposed pulmonary fibrosis (FE). In both groups the peripheral effective airspace dimension (EAD) (E: 0.63 +/- 0.20 mm; FE: 0.60 +/- 0.27 mm, N.S.) was increased by more than a factor of two compared to that of healthy subjects (0.28 +/- 0.05 mm) (p < 0.001). Patients with E showed a significantly higher bolus dispersion than patients with FE (724 +/- 122 cm3 vs. 546 +/- 80 cm3; p < 0.001). However, in patients with FE, bolus dispersion was still significantly higher than in previously published control groups of healthy subjects (546 +/- 80 cm3 vs. 455 +/- 68 cm3; p < 0.001). The results of this study confirm that ADAM and ABD are powerful tools for identifying emphysema even in patients with superimposed pulmonary fibrosis.

Aerosols↗