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- 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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- Cervin, Anders, et al.
(författare)
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Acute exudative inflammation and nasally exhaled nitric oxide are two independent phenomena
- 2002
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Ingår i: ORL. - : S. Karger AG. - 0301-1569 .- 1423-0275. ; 64:1, s. 26-31
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Tidskriftsartikel (refereegranskat)abstract
- Background. Increased levels of nitric oxide (NO) and the exudations of plasma proteins to the airway lumen have both been considered characteristics of airway inflammation. The aim of the present study was to investigate a possible relationship between nasal NO concentrations and acutely induced exudative inflammation of the nasal mucosa. Methods: Twelve healthy non-allergic subjects participated. Nasal challenges with saline, histamine 40 mug/ml (M), histamine 400 mug/ml (H2), oxymethazoline, 0.25 mg/ml (OXY), and a combination of oxymethazoline 0.25 mg/ml and histamine 800 mug/ml (OXYH), were performed on separate occasions. Exhaled NO was measured after each challenge, and alpha(2)-macroglobulin (as a marker of plasma exudation) was measured in nasal lavage fluids after the H 1 and H2 challenges. Results: The mean baseline NO in all measurements was 164 +/- 10.3 ppb. Saline and H1 challenge did not change NO and a2-macroglobulin levels. H2 challenge showed a tendency to reduce NO levels, and the most pronounced decrease was seen after 10 min (-36.3 +/- 16.3%, p = 0.07). This reduction was sustained throughout the registration period. Simultanousley with the decrease in NO, alpha(2)-macroglobulin levels were increased significantly. OXY challenge alone reduced NO significantly throughout the whole registration period. Maximum decrease was seen at 40 min (-21.3 +/- 3.4%, p = 0.03). The OXYH challenge also reduced NO, with a maximal reduction recorded at 10 min (-29.4 +/- 6.4%, p = 0.03). The reduction of NO was sustained throughout the registration period (p < 0.01). Conclusion: Histamine 400 mug/ml induced a prompt plasma exudation response whereas a decrease in nasal NO was registered, suggesting that these two events are not necessarily linked. Furthermore it was shown that the vasoconstrictor oxymethazoline reduced nasal NO, which could be related to reduced mucosal blood flow, whereas the reduction of nasal NO after histamine challenge remains to be elucidated. Copyright (C) 2002 S. Karger AG, Basel.
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- Cervin, Anders, et al.
(författare)
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Nasal Septal Perforations during Treatment with Topical Nasal Glucocorticosteroids Are Generally Not Associated with Contact Allergy to Steroids.
- 2003
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Ingår i: ORL. - : S. Karger AG. - 0301-1569 .- 1423-0275. ; 65:2, s. 103-105
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Mucosal ulcers and perforations of the nasal septum are very rare and may have several underlying causes. Contact allergy to steroids has been suggested as a possible aetiological factor in patients who develop perforations during topical steroid use. <i>Methods:</i> We have identified 13 subjects with perforations of their nasal septum and concomitant topical nasal steroid use. In order to evaluate whether these patients had developed contact allergy to steroids they underwent patch testing with an extended steroid series. <i>Results:</i> None of the subjects displayed any positive reaction to the steroids. <i>Conclusion:</i> Sensitivity to glucocorticoids is a well-described phenomenon and may in selected subjects also be associated with local side effects to nasal sprays. However, contact allergy to steroids does not seem to be a general explanation for septal perforations in patients using nasal steroids.
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- Erjefält, Jonas, et al.
(författare)
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Degranulation patterns of eosinophil granulocytes as determinants of eosinophil driven disease
- 2001
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Ingår i: Thorax. - : BMJ. - 1468-3296 .- 0040-6376. ; 56:5, s. 341-344
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Degranulation of eosinophils in target tissues is considered a key pathogenic event in major chronic eosinophilic diseases. However, because of a lack of appropriate methods, little is known about degranulation of eosinophils in common eosinophilic diseases. METHODS: Using transmission electron microscopic (TEM) analysis, a novel approach has been devised and validated to quantify eosinophil degranulation in human tissues (assessed in individual cells as percentage granules with structural signs of protein release). Biopsy specimens from patients with inflammatory bowel disease, allergic rhinitis, asthma, and nasal polyposis were evaluated. RESULTS: All conditions displayed a similar degree of local tissue eosinophilia, with no differences being observed in eosinophil numbers in the airway mucosa of patients with airway diseases and the colonic mucosa of those with inflammatory bowel disease (IBD). In contrast, marked differences in the mean (SE) extent of eosinophil degranulation were observed between the patient groups; IBD 9.3 (1.4)% altered granules, artificial and natural allergen challenge induced allergic rhinitis 67.8 (6.8)% and 86.6 (3.0)%, respectively, asthma 18.1 (2)%, and nasal polyposis 46.6 (7.6)%. CONCLUSIONS: This study provides the first quantitative data which show that different eosinophilic conditions, despite having similar numbers of tissue eosinophils, may exhibit markedly different degranulation patterns. The present assessment of piecemeal degranulation would thus make it possible to delineate the conditions under which eosinophils are likely to contribute to disease processes. This novel type of analysis may also guide and validate anti-eosinophilic treatment options.
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- Evilevitch, Vladimir, et al.
(författare)
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Microvascular response in guinea pig skin to histamine challenge with and without application of skin window.
- 2004
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 24:5, s. 266-269
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Tidskriftsartikel (refereegranskat)abstract
- We measured the microvascular response to histamine in guinea pig skin. Histamine (40 mg ml-1) was given either as a skin prick test or applied topically onto a skin window. The skin window was prepared by applying suction and gentle warming to the skin so that a blister was formed, and by removing the top of the blister. The microvascular response was measured as the accumulation of radiolabelled transferrin in the skin in vivo, reflecting a combination plasma exudation and vasodilatation. In the control (saline) challenge, the response was slightly greater in the skin window than after skin prick challenge and the scatter was larger. Histamine challenge resulted in a significant microvascular response with respect to the control situation when measured immediately after provocation for both challenge techniques. Ten minutes after challenge, a smaller response was measured, which was still significantly greater than control for the skin prick challenge, but not for topical provocation using the skin window technique. We conclude that the microvascular response to histamine after provocation with the skin prick technique is similar to that after topical provocation using the skin window technique. The skin window technique may have a lower sensitivity than the skin prick technique owing to a higher scatter in the control situation. This difference should be considered when performing and interpreting studies of the microvascular reaction in the skin.
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