| 1. |
- Ahlström-Emanuelsson, Cecilia, et al.
(författare)
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Establishing a model of seasonal allergic rhinitis and demonstrating dose-response to a topical glucocorticosteroid
- 2002
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Ingår i: Annals of Allergy, Asthma & Immunology. - 1081-1206. ; 89:2, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- Background: Symptoms of seasonal allergic rhinitis may vary greatly. Hence, for research purposes, there is a need for disease-like models of allergic rhinitis. In a preliminary study, involving 7 days' challenge with allergen, promising symptom consistency was obtained and dose-response to a glucocorticosteroid could, in part, be demonstrated. Objective: To establish this model of seasonal allergic rhinitis and test the hypothesis that mometasone furoate is more potent than budesonide as an antirhinitis drug. Methods: Thirty-eight patients with seasonal allergic rhinitis received treatment with spray-formulations of placebo, budesonide 64 kg, budesonide 256 mug, and mometasone furoate 200 mug in a double-blind, crossover design. After 3 days' treatment, individualized nasal allergen-challenges were administered daily for 7 days while the treatment continued. Nasal symptoms and peak inspiratory flow (PIF) were recorded. Results: During the last 3 days of allergen challenge without active treatment, consistent around-the-clock symptoms were recorded and recordings during these days were used in the analysis. With few exceptions the active treatments reduced nasal symptoms and improved nasal PIF (P values <0.001 to 0.05). Budesonide caused dose-dependent improvements in evening symptoms, morning nasal PIF, and nasal PIF recorded 10 minutes after allergen-challenge (P values <0.05). Budesonide 256 mug produced greater improvement than mometasone furoate 200 mug for nasal PIF 10 minutes after allergen-challenge (P < 0.05). Conclusion: The present allergen challenge method, producing consistent symptoms and nasal PIF data, emerges as a model of seasonal allergic rhinitis well suited for exploring potency and efficacy of drug intervention. The present data do not support the view that mometasone furoate is a more potent antirhinitis drug than budesonide.
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| 2. |
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| 3. |
- Greiff, Lennart, et al.
(författare)
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Generation of clusters of free eosinophil granules (Cfegs) in seasonal allergic rhinitis
- 1998
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Ingår i: Allergy. - 1398-9995. ; 53:2, s. 200-203
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Tidskriftsartikel (refereegranskat)abstract
- Generation of clusters of free eosinophil granules (Cfegs), through lysis of eosinophils, has recently been proposed as a major paradigm for ultimate activation of airway mucosal eosinophils. In the present study involving patients with seasonal allergic rhinitis, we have investigated whether generation of Cfegs in the nasal mucosa is a feature of allergic rhinitis. Nasal mucosal biopsies were obtained before and late in a birch-pollen season, and were subjected to histochemical staining of eosinophil peroxidase. In biopsies obtained before the pollen season, a few, intact eosinophils were observed, and Cfegs were scarce. In biopsies taken during the pollen season, the numbers of eosinophils were increased about 10-fold (P < 0.05) and the Cfegs about 25-fold (P < 0.05). We conclude that generation of Cfegs is a significant feature of seasonal allergic rhinitis and that this process represents the ultimate activation of mucosal eosinophils in this disease.
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| 4. |
- Greiff, Lennart, et al.
(författare)
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Loss of size-selectivity at histamine-induced exudation of plasma proteins in atopic nasal airways.
- 2002
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 22:1, s. 28-31
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Tidskriftsartikel (refereegranskat)abstract
- Plasma proteins occur in the airway lumen in inflammatory airway diseases. This study tests the hypothesis that airway microvascular-epithelial exudation of plasma proteins, as induced by a non-injurious inflammatory mediator, is characterized by loss of size-selectivity. Using a nasal pool-device, the nasal mucosa of 10 allergic individuals, without current disease, was sequentially exposed to saline and histamine (40 and 400 microg ml(-1)). Nasal lavage fluid and blood-levels of albumin (69 kD) and alpha2-macroglobulin (720 kD) were determined. Histamine produced concentration-dependent exudation of albumin and alpha2-macroglobulin. The albumin/alpha2-macroglobulin concentration ratio of the saline lavage fluid (baseline) was 40+/-19. However, at the histamine challenges the ratios were 25+/-3 and 22+/-2, respectively, which did not differ from that of circulating plasma (22+/-2). We conclude that there is minor and size-selective luminal entry of plasma proteins at baseline. However, at concentration-dependent exudative responses to histamine, plasma proteins enter the airway lumen without being sieved. These data indicate that inflammatory stimulus-induced extravasation, lamina propria distribution and paracellular epithelial passage of plasma occur with minimal size-selectivity. Inferentially, the full immunological capacity of plasma proteins may readily be made available at the surface of human intact airway mucosa.
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| 5. |
- Greiff, Lennart, et al.
(författare)
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Topical nitroprusside may reduce histamine-induced plasma exudation in human nasal airways
- 1995
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 50:7, s. 593-597
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Tidskriftsartikel (refereegranskat)abstract
- Mucosal exudation of nonsieved bulk plasma is a key feature of airway defense and inflammation. We have previously observed in guinea pig tracheobronchial airways that endogenous nitric oxide (NO) of the mucosa may tonically suppress the permeability of the subepithelial microcirculation, and that topical administration of the NO donor nitroprusside may reduce plasma exudation responses. The present study examines whether nitroprusside affects histamine-induced mucosal exudation of plasma in the human nasal airway. In a dose-finding tolerability experiment, using changes in nasal patency as response, placebo and nitroprusside (1.2 and 3.6 mg per nasal cavity) were applied on the mucosal surface with a nasal-spray device. Nasal peak expiratory flow (PEF) rates were measured before the application and thereafter every third minute for 15 min. Nitroprusside produced a dose-dependent decrease in nasal PEF rates compared to placebo. Placebo or nitroprusside (7.2 mg) was then given to the right nasal cavity, followed 3 min later by challenge with saline or histamine (600 micrograms). The drug and the challenge were both applied with a nasal-spray device. With a nasal pool-device, the same large part of the nasal mucosal surface was lavaged before and after the treatment/challenge. The lavage fluid levels of alpha 2-macroglobulin were measured as an index of mucosal exudation of bulk plasma. The histamine-induced lavage fluid level of alpha 2-macroglobulin was significantly higher after treatment with placebo than with nitroprusside. The present data indicate that nitroprusside may have antiexudative effects in human airways. Hence, unlike other microvascular permeability active agents, this pharmacologic principle may be active in both guinea pig and human airways.
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| 6. |
- Persson, Carl, et al.
(författare)
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Airway permeability
- 1995
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222. ; 25:9, s. 807-814
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Forskningsöversikt (refereegranskat)
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| 7. |
- Persson, Carl, et al.
(författare)
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Contribution of plasma-derived molecules to mucosal immune defence, disease and repair in the airways
- 1998
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 47:4, s. 302-313
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Forskningsöversikt (refereegranskat)abstract
- This review discusses recent observations, in health and disease, on the release and distribution of plasma-derived molecules in the airway mucosa. Briefly, the new data on airway mucosal exudation mechanisms suggest that the protein systems of plasma contribute significantly to the mucosal biology, not only in injured airways but also in such mildly inflamed airways that lack oedema and exhibit no sign of epithelial derangement. Plasma as a source of pluripotent growth factor, adhesive, leucocyte-activating, etc., molecules may deserve a prominent position in schemes that claim to illustrate immunological and inflammatory mechanisms of the airway mucosa in vivo.
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| 8. |
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| 9. |
- Persson, Carl, et al.
(författare)
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Plasma-derived proteins in airway defence, disease and repair of epithelial injury
- 1998
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Ingår i: European Respiratory Journal. - 1399-3003. ; 11:4, s. 958-970
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Tidskriftsartikel (refereegranskat)abstract
- One significant characteristic of the airway mucosa in vivo, that cannot easily be mimicked in vitro, is its microcirculation, which generates a highly dynamic, biologically active milieu of plasma-derived molecules that may pass to the airway lumen in vivo. New data on the mechanisms of airway mucosal exudation indicate that the protein systems of circulating plasma may contribute significantly to the biology and immunology of the lamina propria, its surface epithelium and the luminal surface, not only in injured airways, but also in airways that are activated but display no sign of oedema, epithelial disruption, or increased absorption capacity. We suggest that present knowledge of the mechanisms of plasma exudation, together with rapidly emerging information (not detailed herein) on receptors, target cells and cellular responses to the plasma-derived molecules, must be considered in any realistic model that investigates "immuno-inflammatory" mechanisms of the airway mucosa.
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