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  • 1
    Electronic Resource
    Electronic Resource
    Validation of an environmental exposure unit for controlled human inhalation studies with grass pollen in patients with seasonal allergic rhinitis (2003)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 33 (2003), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background There is an increasing need for allergen inhalation systems to perform basic clinical research and test anti-allergic drugs under well-controlled conditions. This requires stability of environmental conditions like temperature and humidity, as well as allergen concentration and reproducible induction of allergic symptoms.Objective The aim of this study was to validate an environmental exposure unit for controlled human pollen inhalation studies in participants with seasonal allergic rhinitis.Methods Temperature, relative humidity, and air flow rate were kept constant with an air conditioning system. Pollen atmosphere was generated using a specially designed feeding system and monitored online by laser counter and offline using rotating rod samplers. Efficacy (total nasal symptom score, nasal air flow rate, nasal secretion) and safety (lung function) parameters were evaluated at different pollen concentrations and repeated allergen challenges.Results Temperature, humidity, and air flow rate in the environmental exposure unit remained constant within a range of 〈2%. The spatial distribution and the temporal stability of the pollen concentration varied only slightly over 4 h (±10% and 〈4%, respectively). Dose-dependent induction of allergic rhinitis symptoms, reduction in nasal air flow rate, and increase in nasal secretion were observed over time. These effects were reproducible from day to day. Lung function remained clinically normal at all concentrations and from day to day.Conclusions Thus, pollen exposure in the environmental exposure unit is an effective, reproducible, safe, and suitable method for single-centre clinical studies on the efficacy of anti-allergic treatment or basic clinical research.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2003.01810.x
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  • 2
    Electronic Resource
    Electronic Resource
    Local release of eosinophil peroxidase following segmental allergen provocation in asthma (2003)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 33 (2003), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Eosinophil peroxidase (EPO) is an eosinophilic basic protein, which leads to increased permeability and damage of bronchial epithelial cells in asthma.Objective As little is known about its local expression and release in humans the intracellular expression in lung and peripheral eosinophils and the concentrations of EPO in bronchoalveolar lavage (BAL) fluid and serum was investigated in patients with asthma.Methods Twelve mild atopic asthmatic and nine control subjects underwent segmental sham and allergen challenge. EPO concentrations in BAL fluid and serum were determined by immunoassay and flow cytometry was used to determine the intracellular expression of EPO in BAL-derived and peripheral eosinophils.Results In asthmatic patients a large increase in BAL eosinophils – total cells: median 9.5 × 106 (range: 0.5 to 455.0 × 106); relative: 38% (1 to 91%) – was detectable 24 h following allergen challenge, but peripheral blood eosinophil counts did not change. Concentrations of EPO in BAL fluid increased from 1 µg/L (1.0 to 6.8 µg/L) to 42 µg/L (5.6 to 379.6 µg/L; P 〈 0.01) after allergen but not after saline challenge (1.5 µg/L; 1.0 to 21.9 µg/L), whereas in control subjects all measurements were below the detection limit. Serum concentrations of EPO increased slightly from 18.3 µg/L (3.0 to 56.8 µg/L) to 27 µg/L (3.8 to 133.9 µg/L; P 〈 0.05) 24 h after allergen challenge in asthmatic patients. Furthermore, the intracellular expression of EPO (measured as mean fluorescence intensity) was decreased in BAL eosinophils compared with blood eosinophils (mean fluorescence intensity 29 (7 to 71) vs. 48 (20 to 85); P 〈 0.01) after allergen challenge.Conclusion The finding of increased EPO concentrations in the BAL fluid and decreased intracellular EPO expression in pulmonary eosinophils of asthmatic patients reflects the allergen-triggered release of EPO into the bronchial space.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2003.01580.x
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  • 3
    Electronic Resource
    Electronic Resource
    The Th2 cell in asthma: initial expectations yet to be realised (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 27 (1997), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1997.tb00685.x
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of loteprednol etabonate nasal spray suspension on seasonal allergic rhinitis assessed by allergen challenge in an environmental exposure unit (2005)
    Oxford, UK : Munksgaard International Publishers
    Allergy 60 (2005), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Loteprednol etabonate (LE) is a novel soft steroid that was designed to improve the benefit/risk ratio of topical corticosteroid therapy. This study assesses the clinical efficacy and safety of three different doses of LE nasal spray in seasonal allergic rhinitis (SAR).Methods:  In this single-center, double-blind, placebo-controlled, parallel-group trial 165 subjects with SAR to grass pollen received daily single doses of either 100, 200, 400 μg LE nasal spray, or placebo for 14 days. The patients underwent three 4-h allergen challenges with grass pollen in an environmental exposure unit at a screening visit (baseline) and on days 7 and 14 of treatment. Standardized nasal symptom scores were obtained every 20 min. Nasal flow, nasal secretions, and FEV1 were measured every hour during allergen challenges.Results:  After 14 days of treatment, patients who received 400 μg LE had significantly lower total nasal symptom scores compared with those receiving placebo (P = 0.007). LE400 reduced rhinorrhea, nasal congestion, nasal itching, the amount of nasal secretions, and improved nasal flow as compared with placebo (P 〈 0.05). LE100 and LE200 were not significantly different from placebo. All treatments were well tolerated.Conclusions:  Loteprednol 400 μg once daily is superior to placebo and the only effective dose tested in improving nasal symptoms and objective parameters in patients with SAR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.2005.00703.x
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  • 5
    Electronic Resource
    Electronic Resource
    Effect of anti-nerve growth factor on early and late airway responses in allergic rats (2003)
    Oxford, UK : Munksgaard International Publishers
    Allergy 58 (2003), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: The increased production of nerve growth factor (NGF) has been associated with allergen-induced airway hyperresponsiveness and enhanced airway inflammation in experimental models of asthma. The aim of this study was to investigate whether a local application of anti-NGF to the lungs may affect the allergen-specific early (EAR) and late (LAR) airway responses to ovalbumin (Ova) of Ova-sensitized brown Norway rats.Methods: Rats were sensitized systemically with Ova and were boosted twice intratracheally with Ova aerosol using a microsprayer. Two hours before every boost, the animals were pretreated either with aerosolized anti-NGF or with a control antibody. On day 21, all animals were challenged with inhalational Ova aerosol and pulmonary resistance was recorded in anesthetized, orotracheally intubated animals during the early and late asthmatic responses. In addition, differential cell counts from bronchoalveolar lavage and serum immunoglobulin E (IgE) levels were determined 48 h post-Ova challenge.Results: Pretreatment with anti-NGF significantly attenuated the EAR but had no significant effect on the LAR. Serum IgE levels and inflammatory cell influx into the lungs were not affected by anti-NGF pretreatment.Conclusion: The data from this study suggest that NGF is directly involved in the development of the EAR without affecting the inflammatory airway response or LAR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1398-9995.2003.00208.x
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  • 6
    Electronic Resource
    Electronic Resource
    Pulmonary uptake of bupivacaine in isolated perfused rat lung (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 351 (1995), S. 99-106 
    Details
    ISSN: 1432-1912
    Keywords: Lung perfusion ; Bupivacaine ; Fluorochrome-labeled capillaries ; First-pass retention ; Inulin ; Tritium-labeled water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ability of rat lung to remove the local anaesthetic drug bupivacaine from the blood was studied in isolated organs which were perfused either in an open (single-pass mode) or in a closed system (recirculating medium). Isolated perfused rat lungs exhibited a very low capacity to metabolize bupivacaine within 3 h during which the drug circulated continuously through the organ. The clearance values differed only by 0.2 ml/min from the control parameters in sham perfusions. The calculated extraction ratio was 0.2% and the elimination half-life was about 210 min. The volume of distribution of bupivacaine was 133 ml which remarkably surmounted the reference values obtained for sham perfusions. The distribution of bupivacaine into the pulmonary tissue was investigated applying the multiple indicator dilution technique to isolated lungs perfused in the single-pass mode. The mean elimination time of model compounds for distribution into the intravascular space, 14C-inulin, and the total water space, 3H-water, were 68 and 75 s at a flow rate of 6 ml/min. The volume of distribution was 5.9 ml for inulin and 6.5 ml for water. The mean transit time for concomitantly injected bupivacaine was 221 s and the volume of distribution was 14.4 ml. The respective parameters of sham perfusions performed without an isolated organ were substantially lower, i.e. mean elimination time 50, 50 and 61 s and distribution volume 4.9, 5.0 and 6.1 ml for inulin, water and bupivacaine. The volume of distribution during single-pass contact of bupivacaine to lung was not substantially influenced by an increase of the flow rate from 6 to 9 and 12 ml/min whereas the mean transit time dropped from 221 to 121 and 108 s, respectively. These results support the assumption that bupivacaine is extensively retained by the pulmonary tissue and that elimination of bupivacaine by metabolism can be neglegted for lung. The hemodynamic parameters of bronchiolar perfusion in the artificially perfused lung were determined using two fluorochrome-labeled macromolecular proteins, i.e. fluorescein-isothiocyanate (FITC)- and lissamine-rhodamine-B 200 (RB 200)-labeled globulin. After 10 min of perfusion at a flow rate of 12 ml/min in the closed system an area of 10.8070 of the peribronchiolar tissue area contained the dye-label FITC. A very similar index (10.1%) of dye-coloured capillaries was obtained when the lungs of anaesthetized rats were examined 10 min after intravenous injection of the fluorochrome into the pulmonary artery in vivo. In isolated perfused rat lungs receiving both FITC and RB 200 59.5% of FITC-labeled capillaries were reached by the second fluorochrome within 2 s. This fraction accounted for 93.3% after 10 s of circulation time. This proves that isolated rat lungs were well perfused in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169070
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  • 7
    Electronic Resource
    Electronic Resource
    Pulmonary uptake of bupivacaine in isolated perfused rat lung (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 351 (1994), S. 99-106 
    Details
    ISSN: 1432-1912
    Keywords: Key words Lung perfusion ; Bupivacaine ; Fluorochrome-labeled capillaries ; First-pass retention ; Inulin ; Tritium-labeled water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ability of rat lung to remove the local anaesthetic drug bupivacaine from the blood was studied in isolated organs which were perfused either in an open (single-pass mode) or in a closed system (recirculating medium). Isolated perfused rat lungs exhibited a very low capacity to metabolize bupivacaine within 3 h during which the drug circulated continuously through the organ. The clearance values differed only by 0.2 ml/min from the control parameters in sham perfusions. The calculated extraction ratio was 0.2% and the elimination half-life was about 210 min. The volume of distribution of bupivacaine was 133 ml which remarkably surmounted the reference values obtained for sham perfusions. The distribution of bupivacaine into the pulmonary tissue was investigated applying the multiple indicator dilution technique to isolated lungs perfused in the single-pass mode. The mean elimination time of model compounds for distribution into the intravascular space, 14C-inulin, and the total water space, 3H-water, were 68 and 75 s at a flow rate of 6 ml/min. The volume of distribution was 5.9 ml for inulin and 6.5 ml for water. The mean transit time for concomitantly injected bupivacaine was 221 s and the volume of distribution was 14.4 ml. The respective parameters of sham perfusions performed without an isolated organ were substantially lower, i.e. mean elimination time 50, 50 and 61 s and distribution volume 4.9, 5.0 and 6.1 ml for inulin, water and bupivacaine. The volume of distribution during single-pass contact of bupivacaine to lung was not substantially influenced by an increase of the flow rate from 6 to 9 and 12 ml/min whereas the mean transit time dropped from 221 to 121 and 108 s, respectively. These results support the assumption that bupivacaine is extensively retained by the pulmonary tissue and that elimination of bupivacaine by metabolism can be neglegted for lung. The hemodynamic parameters of bronchiolar perfusion in the artificially perfused lung were determined using two fluorochrome-labeled macromolecular proteins, i.e. fluorescein-isothiocyanate (FITC)- and lissamine-rhodamine-B 200 (RB 200)-labeled globulin. After 10 min of perfusion at a flow rate of 12 ml/min in the closed system an area of 10.8% of the peribronchiolar tissue area contained the dye-label FITC. A very similar index (10.1%) of dye-coloured capillaries was obtained when the lungs of anaesthetized rats were examined 10 min after intravenous injection of the fluorochrome into the pulmonary artery in vivo. In isolated perfused rat lungs receiving both FITC and RB 200 59.5% of FITC-labeled capillaries were reached by the second fluorochrome within 2 s. This fraction accounted for 93.3% after 10 s of circulation time. This proves that isolated rat lungs were well perfused in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169070
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    Paper (German National Licenses)
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