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  • 1
    Electronic Resource
    Electronic Resource
    Twelve months, treatment with inhaled salmeterol in asthmatic patients (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 47 (1992), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Salmeterol is a new β2-receptor agonist with a prolonged duration of action after inhalation, exceeding 12 h in most patients. We have performed a 12-month open follow-up study on 11 patients with reversible asthma. All patients were given salmeterol inhalations (50 μg twice daily). Additional asthma treatment included inhaled corticosteroids in all patients, and oral slow-release theophylline or β2-receptor agonists in a minority of patients (3 and 1, respectively). Before salmeterol treatment was initiated and after 3, 6, 9 and 12 months of salmeterol treatment, a cumulative dose-response curve to inhaled salbutamol (100, 300 and 900 μg) was performed, and FEV1 measured. We also evaluated the effect of each salbutamol dose on finger tremor, systemic blood pressure and heart rate. Blood tests, including white blood count and electrolytes, were taken at each visit. After salmeterol treatment was initiated, morning FEV1, measured before the morning asthma medication, was significantly improved (p〈0.05). The responsiveness to inhaled salbutamol was not decreased during salmeterol treatment, except in one patient with asthma worsening over the study year. Baseline finger tremor measured before salbutamol dose-response curves, was significantly lower at the 12-month visit than before treatment was initiated (p〈0.05). Effects of salbutamol on systemic blood pressure, heart rate or finger tremor was not significantly changed during salmeterol treatment. We found a successive and significant decrease in blood eosinophils (p〈0.05) during the 12 months of salmeterol treatment, when the patient with asthma worsening was excluded in the analysis. Also platelet count was significantly decreased during the treatment period (p〈 0.001), although within the normal range for all patients. In the present study, we found no evidence that long-term treatment with inhaled salmeterol (50 μg twice daily) produced decreased β2-receptor sensitivity in airways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1992.tb00668.x
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  • 2
    Electronic Resource
    Electronic Resource
    Ovalbumin aerosol challenge in actively sensitized guinea pigs: relationship between airway microvascular leakage and airflow obstruction (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 47 (1992), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Airway inflammation is a common feature of asthma, and one of the cardinal features of inflammation is increased microvascular permeability. We investigated the characteristics of inhaled ovalbumin challenge-induced airflow obstruction and airway microvascular leakage in vivo in mechanically ventilated guinea pigs actively sensitized to ovalbumin. A method was used to quantify both airflow obstruction and airway microvascular leakage in order to investigate the relationship between these 2 pathophysiological features in the same animal. Airway microvascular leakage was assessed by Evans blue dye extravasation into airway tissues. Actively sensitized guinea pigs developed both acute airflow obstruction (increased lung resistance and reduced dynamic lung compliance) and Evans blue dye extravasation in response to exposure to aerosolised ovalbumin. Evans blue dye extravasation was preferentially distributed in the distal airways and correlated with airflow obstruction. The results show that inhaled allergen induced both acute airflow obstruction and airway microvascular leakage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1992.tb00677.x
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  • 3
    Electronic Resource
    Electronic Resource
    Upregulation of nasal mucosal eotaxin in patients with allergic rhinitis during grass pollen season: effect of a local glucocorticoid (2000)
    Oxford BSL : Blackwell Science Ltd
    Clinical & experimental allergy 30 (2000), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Allergic rhinitis is a common disease characterized by infiltration of eosinophils into the nasal mucosa during the periods of symptoms. Among chemokines, which attract cells to the site of inflammation, eotaxin is relatively specific for eosinophils.〈section xml:id="abs1-2"〉〈title type="main"〉ObjectiveWe examined the influence of grass pollen season on nasal eotaxin expression in patients with seasonal allergic rhinitis, as well as the effect of a nasal glucocorticoid on this eotaxin expression.〈section xml:id="abs1-3"〉〈title type="main"〉MethodsNineteen patients with allergic rhinitis received treatment with either nasal beclomethasone (400 μg/day) or placebo over a grass pollen season. In these patients, nasal biopsies were taken prior to and during the peak of the pollen season and stained immunohistochemically for eotaxin and EG2 + eosinophils. Five healthy subjects served as controls and gave nasal biopsies once prior to the pollen season.〈section xml:id="abs1-4"〉〈title type="main"〉ResultsPrior to pollen season, there was no significant difference in nasal eotaxin expression between patients with allergic rhinitis and healthy subjects. Grass pollen season induced significant increase in eotaxin expression in placebo-treated (P = 0.04; n = 9) but not in beclomethasone-treated rhinitis patients (P = 0.8; n = 10). During peak grass pollen season, the eotaxin expression in placebo-treated patients was significantly higher compared with healthy subjects outside season (P = 0.03). There was no significant correlation between the expression of eotaxin and the number of EG2 + eosinophils in nasal mucosa. The serum levels of eotaxin in rhinitis patients remained stable over the pollen season.〈section xml:id="abs1-5"〉〈title type="main"〉ConclusionExpression of eotaxin in nasal mucosa of grass-pollen allergic rhinitis patients is upregulated during pollen season and treatment with a nasal glucocorticoid protects against this upregulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2000.00993.x
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  • 4
    Electronic Resource
    Electronic Resource
    Increased number of CD34+cells in nasal mucosa of allergic rhinitis patients: inhibition by a local corticosteroid (2005)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 35 (2005), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Eosinophils develop from CD34+ haematopoietic progenitor cells. Allergen exposure in susceptible individuals is known to induce a local eosinophilic inflammation, but the effect on progenitor cells is much less understood.Objective We aimed to evaluate how allergen exposure affects the number of tissue CD34+ cells and CD34+ eosinophils in allergic rhinitis (AR) patients and whether any such effect is influenced by local corticosteroid treatment. Also, we evaluated changes in the number of CXC receptor 4-positive cells (CXCR4+), since the CXCR4 ligand (stromal cell-derived factor-1 (SDF-1)) is a potent chemoattractant for haematopoietic progenitors.Methods In a double-blind, randomized study, pollen-sensitized AR patients were treated with a nasal corticosteroid fluticasone propionate (FP, 200 μg/day) or placebo throughout the pollen season. Nasal biopsies were taken before and during the season. CD34 and CXCR4 were stained using immunohistochemistry.Results The pollen season significantly increased the number of CD34+ cells, CD34+/CXCR4+ cells and CD34+ eosinophils in placebo-treated patients, but not in FP-treated patients. The mean pollen season-induced increase in CD34+ cells, CD34+/CXCR4+ cells and CD34+ eosinophils in FP-treated patients was lower compared with placebo-treated patients.Conclusion A pollen season increases the number of CD34+ cells in nasal tissue accompanied by an increase in the number of CD34+/CXCR4+ haematopoietic progenitors and also the number of CD34+ eosinophils in subjects with AR. Treatment with a local corticosteroid provides protection against this pollen-induced increase in tissue CD34+ cells and CD34+ eosinophils possibly via inhibition of allergen-induced CXCR4-mediated recruitment of CD34+ haematopoietic progenitors into airways and their further differentiation into eosinophils within the tissue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2004.02038.x
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  • 5
    Electronic Resource
    Electronic Resource
    Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma (2004)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 34 (2004), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Patients with severe asthma are often inadequately controlled on existing anti-asthma therapy, constituting an unmet clinical need.Objective This randomized, double-blind, placebo-controlled trial evaluated the ability of omalizumab, a humanized monoclonal anti-IgE antibody, to improve disease control sufficiently to enable inhaled corticosteroid reduction in patients with severe allergic asthma.Methods After a run-in period when an optimized fluticasone dose (〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:09547894:CEA1916:ges" location="ges.gif"/〉1000 μg/day) was received for 4 weeks, patients were randomized to receive subcutaneous omalizumab [minimum 0.016 mg/kg/IgE (IU/mL) per 4 weeks; n=126] or matching placebo (n=120) at intervals of 2 or 4 weeks. The study comprised a 16-week add-on phase of treatment followed by a 16-week fluticasone-reduction phase. Short-/long-acting β2-agonists were allowed as needed.Results Median reductions in fluticasone dose were significantly greater with omalizumab than placebo: 60% vs. 50% (P=0.003). Some 73.8% and 50.8% of patients, respectively, achieved a 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:09547894:CEA1916:ges" location="ges.gif"/〉50% dose reduction (P=0.001). Fluticasone dose reduction to 〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:09547894:CEA1916:les" location="les.gif"/〉500 μg/day occurred in 60.3% of omalizumab recipients vs. 45.8% of placebo-treated patients (P=0.026). Through both phases, omalizumab reduced rescue medication requirements, improved asthma symptoms and asthma-related quality of life compared to placebo.Conclusion Omalizumab treatment improves asthma control in severely allergic asthmatics, reducing inhaled corticosteroid requirements without worsening of symptom control or increase in rescue medication use.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2004.1916.x
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  • 6
    Electronic Resource
    Electronic Resource
    Role of eicosanoids in airflow obstruction and airway plasma exudation induced by trimellitic anhydride-conjugate in guinea-pigs 3 and 8 weeks after sensitization (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 24 (1994), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract. Trimellitic anhydride (TMA) is a low molecular weight chemical which can cause occupational asthma. We studied the role of eicosanoids in airway responses to TMA at different times after sensitization in actively sensitized guinea-pigs. Sensitization was performed by two intradermal injections of free TMA (0.1 ml of 0.3% TMA in corn oil). At 3 and 8 weeks after sensitization, the guinea-pigs were anaesthetized and challenged with intratracheal instillation of 0.5% TMA conjugated to guinea-pig serum albumin (TM A-GPSA; 50 μl). Lung resistance (RL) was measured to assess airflow obstruction, and the tissue content of Evans Blue dye was measured to assess airway plasma exudation. Intratracheal instillation of TMA-GPSA induced a slowly progressing increase in RL, reaching a peak at approximately 3.5 min after the challenge (6.0 ± 2.0cm H2O/ml/s in the 3-week group and 3.8 + 0.6 in the 8-week group). Pretreatment before challenge with pyrilamine (anti-histamine: 2 mg/kg. intravenously) slowed the onset of the increase in RL following challenge with TMA-GPSA, and significantly attenuated the peak response. A combination of pyrilamine and IC1-192, 605 (thromboxane receptor antagonist; 0.5 mg/kg, intravenously) completely abolished the increase in RLin both week groups. A combination of pyrilamine and ICI-198, 615 (leukotrieneC4/D4/ E4 receptor antagonist: 0.5 mg/kg, intravenously) did not further attenuate the increase in RL compared with pretreatment with pyrilamine alone, but the induced Evans Blue dye extravasation was completely inhibited in the 3-week group, whereas a remaining extravasation was observed in the 8-week group. We conclude that the bronchoconstrictor response to TMA-GPSA in actively sensitized guinea-pigs is mediated by histamine and thromboxane A2 both early and late after sensitization, whereas leukotrienes and histamine partially mediate TMA-induced airway plasma exudation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1994.tb00956.x
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  • 7
    Electronic Resource
    Electronic Resource
    Glucocorticoids and immunoglobulin E: no new in vivo paradigms (2002)
    Oxford, UK : Blackwell Science, Ltd
    Clinical & experimental allergy 32 (2002), 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/10.1046/j.1365-2222.2002.01336.x
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  • 8
    Electronic Resource
    Electronic Resource
    Inflammatory remonses in skin and airways after allergen challenge in brown Norway rats sensitrzed to trimvellitic anhydride (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 51 (1996), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Trimellitic anhydride (TMA) is a low-molecular-weight compound which causes occupational allergy. Brown Norway rats were sensitized to TMA injected intradermally (0.3% TMA suspended in oil). Three weeks later, we examined responses to either free TMA injected intradermally, or TMA conjugated to rat serum albumin (TMA-RSA) given by inhalation (0.5%, nebulized for 15 min). Twenty-one days after the sensitization, Evans blue dye was given i.v. (20 mg/kg), and extravasation of dye in skin was measured 30 min after oil or TMA injections (0.03–10% in oil). In a separate series of experiments, we evaluated the accumulation of eosinophils in the skin after single and repeated injections of TMA (0.03–0.3%). The injection sites were removed and fixed in formalin 18–24 h after the last injection. In a third series of experiments, we evaluated the effects of airway exposure to TMA-RSA (0.5% in 0.9% saline) on the accumulation of eosinophils in the bronchial wall counted with quantitative light microscopy. Intradermal injections of free TMA caused a dose-dependent increase of Evans blue dye extravasation which was significantly higher in sensitized animals than in controls. Skin histology revealed a significant and dose-dependent increase in eosinophils after repeated TMA injections in sensitized animals. Exposure to aerosolized TMA-RSA caused a significant increase of eosinophils in the bronchial wall of sensitized rats compared with nonsensitized rats. Sensitized animals showed significantly higher levels of specific IgG and IgE. We conclude that brown Norway rats can be used as a model of TMA-induced allergic inflammation, mimicking occupational asthma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1996.tb04668.x
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  • 9
    Electronic Resource
    Electronic Resource
    Capsaicin pretreatment does not inhibit allergen-induced airway microvascular leakage in guinea pig (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 46 (1991), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have studied the effects of tachykinin-depletion on airway microvascular leakage induced by allergen challenge in ovalbumin-sensitised guinea pigs, Tachykinin-depletion was obtained by capsacin pretreatment 1 week before inhaled allergen challenge. Capsaicin pretreatment did not change airway microvascular permeability induced by allergen challenge. Capsaicin pretreatment did not change airway microvascular permeability induced by allergen challenge. Thus, sensory neuropeptides may not be important in allergen induced acute airway microvascular leakage in guinea pig in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1991.tb00552.x
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  • 10
    Electronic Resource
    Electronic Resource
    Differential effects of fluticasone and montelukast on allergen-induced asthma (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: Early asthmatic responses (EAR) and late asthmatic responses (LAR) to allergen are induced by the local release of a series of bronchoconstrictor mediators, including leukotrienes and histamine. Both anti-leukotrienes and other anti-asthma drugs, such as inhaled glucocorticoids, have been shown to reduce both EAR and LAR. The aim of the present study was to directly compare the effects of regular treatment with an oral anti-leukotriene, montelukast (Mont; 10 mg once daily, for 8 days), and an inhaled glucocorticoid [fluticasone propionate (FP) 250 μg twice daily for 8 days] on the EAR and LAR to an inhaled allergen challenge. Patients with a documented EAR and LAR at a screening visit were randomized to these treatments, or placebo, in a double-blind, double-dummy, crossover fashion. Allergen challenge at a dose causing both an EAR and LAR was given on the eighth day of treatment. The maximum fall in FEV1 during the EAR was 17.8% during placebo treatment, 8.3% during Mont and 16.3% during FP (P 〈 0.05 for Mont vs placebo). The maximum fall during the EAR was 13.8% during placebo treatment, 11.8% during Mont and 2% during FP treatment (P 〈 0.05 for FP vs placebo and FP vs Mont). PC20 methacholine was significantly higher 24 h after allergen challenge during FP-treatment compared with Mont (P 〈 0.05). Both montelukast and fluticasone reduced the relative amount of sputum eosinophils after allergen compared with placebo treatment. This study shows that anti-leukotrienes are effective to attenuate the EAR, whereas inhaled glucocorticoids are more effective than anti-leukotrienes in attenuating the EARs and improves bronchial hyperresponsiveness to a greater extent. In conclusion, inhaled glucocorticoids have overall greater efficacy than oral anti-leukotrienes to attenuate allergen-induced airway responses in mild asthmatic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.2005.00633.x
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